Scientific publications by MedGenome and featuring MedGenome services

Results of comprehensive genetic testing in patients presenting to a multidisciplinary inherited heart disease clinic in India

Indian Heart J, 2024

PMID: 39009076

The study analyzed the outcomes of comprehensive genetic testing in patients at a multidisciplinary inherited heart disease clinic in India from August 2017 to October 2023. It included 77 subjects (48 probands, 29 relatives) with an average age of 43 years, 68% male, and 44% symptomatic, spanning various conditions such as hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic cardiomyopathy, peripartum cardiomyopathy, congenital long QT syndrome, Brugada syndrome, and Marfan Syndrome. Next-generation sequencing (NGS) was employed, with a 31% diagnostic yield, 54% identifying variants of uncertain significance (VUS), and 15% being genotype-negative. Genetic testing guided follow-up and treatment, with periodic monitoring recommended for genotype-positive and high-risk VUS carriers, while others were discharged from further surveillance. The study highlights the importance of genetic testing in specialized clinics for effective management and family screening in inherited heart diseases.

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CNS-wide repopulation by hematopoietic-derived microglia-like cells corrects progranulin deficiency in mice

Nat Commun, Vol 15, Issue 1, Article No. 5654

PMID: 38969669

Hematopoietic stem cell transplantation can deliver therapeutic proteins to the central nervous system (CNS) through transplant-derived microglia-like cells. However, current conditioning approaches result in low and slow engraftment of transplanted cells in the CNS. Here we optimized a brain conditioning regimen that leads to rapid, robust, and persistent microglia replacement without adverse effects on neurobehavior or hematopoiesis. This regimen combines busulfan myeloablation and six days of Colony-stimulating factor 1 receptor inhibitor PLX3397. Single-cell analyses revealed unappreciated heterogeneity of microglia-like cells with most cells expressing genes characteristic of homeostatic microglia, brain-border-associated macrophages, and unique markers. Cytokine analysis in the CNS showed transient inductions of myeloproliferative and chemoattractant cytokines that help repopulate the microglia niche. Bone marrow transplant of progranulin-deficient mice conditioned with busulfan and PLX3397 restored progranulin in the brain and eyes and normalized brain lipofuscin storage, proteostasis, and lipid metabolism. This study advances our understanding of CNS repopulation by hematopoietic-derived cells and demonstrates its therapeutic potential for treating progranulin-dependent neurodegeneration.

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Phenotype-Genotype Correlation of a Cohort of Patients with Congenital Myopathy: A Single Centre Experience from India

J Neuromuscul Dis, Pages 1-23, 2024

PMID: 38968056

This study describes the clinical and histopathological characteristics of genetically confirmed congenital myopathies (CMs) in India, aiming to establish phenotype-genotype correlations. A retrospective chart review of patients from January 2016 to December 2020 was conducted, involving 31 unrelated patients (14 males, 17 females) with a median age at onset of 2.0 years and illness duration of 6.0 years. Clinical features included proximodistal weakness (54.8%), facial weakness (64.5%), myopathic facies (54.8%), ptosis (33.3%), and ophthalmoplegia (19.4%). Muscle histopathology, available for 38.7%, most frequently showed centronuclear myopathy. Pathogenic genetic variants were identified in RYR1 (29.0%), DNM2 (19.4%), SELENON (12.9%), KBTBD13 (9.7%), NEB (6.5%), and MYPN (6.5%), with novel mutations in 30.3% of the cohort. Follow-up data for 77.4% showed a median duration of 4.5 years and age of 13 years at last follow-up, with most patients ambulant with minimal assistance. Mortality was 8.3%, mainly due to respiratory failure in centronuclear myopathy 1 and congenital myopathy 3 with rigid spines (SELENON).

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Clinical exome sequencing unravels the diverse spectrum of genetic heterogeneity and genotype-phenotype correlations in hypertrophic cardiomyopathy

Int J Cardiol, Vol. 411, Article Number: 132273, 2024

PMID: 38880420

Catalogs of pathogenic mutations in hypertrophic cardiomyopathy (HCM) are limited for the South Asian population despite their higher heart disease risk. This study sequenced 200 HCM patients, finding a 40% yield for pathogenic or likely pathogenic (P/LP) variants, primarily in MYBPC3 and MYH7 genes. Key predictors of positive genetic tests included younger age at diagnosis, family history, specific echocardiographic patterns, and absence of hypertension. MYBPC3 variants were linked to severe outcomes like ventricular tachycardia, while MYH7 variants were associated with specific cardiac dimensions. The study underscores the enrichment of rare P/LP variants and variants of uncertain significance (VUSs) in HCM cases, enhancing targeted genetic testing for this population.

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Early detection and diagnosis of cancer with interpretable machine learning to uncover cancer-specific DNA methylation patterns

Biol Methods Protoc, Vol. 9, Issue 1, Article Number: bpae028, 2024

PMID: 38903861

In this study, the authors present an interpretable machine learning model that can classify 13 cancer types and non-cancer tissue samples using only DNA methylome data, achieving 98.2% accuracy. The features identified by this model are utilized to develop EMethylNET, a robust framework consisting of an XGBoost model that informs a deep neural network, capable of generalizing to independent data sets. The authors also demonstrate that the methylation-associated genomic loci detected by the classifier are linked to genes, pathways, and networks involved in cancer, providing insights into the epigenomic regulation of carcinogenesis.

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Cystatin F a potential diagnostic biomarker in acute promyelocytic leukemia

Ann Hematol, Vol. 103, Issue 6, Pages 2181-2183, 2024

PMID: 38427058

There are limitations with morphology and a felt need for a diagnostic test with a short turn-around time for rapid diagnosis of acute promyelocytic leukemia (APL). To identify a unique protein biomarker in APL, we did a quantitative proteomic analysis on five acute myeloid leukemia (AML), APL and acute lymphoblastic leukemia (ALL) bone marrow mononuclear cells (MNCs) collected at diagnosis in comparison with peripheral blood mononuclear cells from healthy control (HC).

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Comprehensive germline profiling of patients with breast cancer: initial experience from a Familial Cancer Clinic.

Ecancermedicalscience, Vol. 18, Article No.1670, 2024

PMID: 38439815

Breast cancer is the most common cancer among Indian females. There is limited data on germline profiling of breast cancer patients from India. The objective of the current study was to analyse the frequency and spectrum of germline variant profiles and clinicopathological characteristics of breast cancer patients referred to our Familial Cancer Clinic (FCC). All patients underwent pretest counselling. Genetic testing was done by multigene panel testing by next-generation sequencing along with reflex multiplication ligation-dependent probe amplification for BRCA1 and 2. We report a 41% pathogenic/likely pathogenic (P/LP) variant rate in our selected cohort of breast cancer patients, with variants in BRCA constituting 83% and non-BRCA gene variants constituting 17%.

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Optimization and Validation of a Harmonized Protocol for Generating Therapeutic-Grade Dendritic Cells in a Randomized Phase II Clinical Trial, Using Two Varied Antigenic Sources.

Vaccines (Basel), Vol. 12, Issue 2, Article No.112, 2024

PMID: 38400096

Autologous dendritic cell (DC)-based immunotherapy is a cell-based advanced therapy medicinal product (ATMP) that was first introduced more than three decades ago. In the current study, our objective was to establish a harmonized protocol using two varied antigenic sources and a good manufacturing practice (GMP)-compliant, manual method for generating clinical-grade DCs at a limited-resource academic setting. Our results confirm that the manual/semi-automated protocol was simple, consistent, and cost-effective, without the requirement for expensive equipment and without compromising on the quality of the final product.

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Acute lymphoblastic leukemia with myeloid mutations is a high-risk disease associated with clonal hematopoiesis

Blood Cancer Discov, 2023

PMID: 38150184

Myeloid neoplasms arise from pre-existing clonal hematopoiesis (CH), however the role of CH in pathogenesis of ALL is unknown. By using single cell proteogenomic analysis, we demonstrated that myeloid mutations were present years before the diagnosis of ALL, and a subset of these clones expanded over time to manifest as dominant clones in ALL. Single cell RNA-sequencing revealed upregulation of genes associated with cell survival and resistance to apoptosis in B-ALL with MyM, which responds better to newer immunotherapeutic approaches.

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Predicting outcomes in esophageal adenocarcinoma following neoadjuvant chemoradiation: Interactions between tumor response and survival

J Thorac Cardiovasc Surg, Vol. S0022-5223, Issue 23, Pages 01091-01097, 2023

PMID: 37967764

The prognostic value of tumor regression scores (TRS) in patients with esophageal adenocarcinoma (EAC) who underwent neoadjuvant chemoradiation remains unclear. We sought to investigate the prognostic value of pathologic and metabolic treatment response among EAC patients undergoing neoadjuvant chemoradiation. Patients with pathologic complete response had prolonged OS, whereas no difference in survival was detected among other TRS categories. At initial staging, the presence of signet ring cells and greater SUV uptake at regional lymph nodes predicted residual disease at pathology and shorter OS, suggesting the need for new treatment strategies for these patients.

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Diagnostic exome identifies a novel PRKG2 mutation in a proband with skeletal dysplasia.

Clinical Genetics, December 2023

This graphic abstract combines pedigree, dysmorphology features, radiographs, and the PRKG2 protein domain, specifically the CNB-A regulatory domain, which harbors a mutation resulting in premature protein termination.

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Neonatal Ichthyosis and sclerosing cholangitis (NISCH) syndrome with a novel Claudin-1 (CLDN1) mutation: A report from India

Indian Journal of Dermatology, Venereology and Leprology, August 2023

Mutations in the Claudin-1 (CLDN1, Gene ID: 9076) gene are known to result in the autosomal-recessive neonatal ichthyosis-sclerosing cholangitis (NISCH) syndrome (OMIM: 607626).1 The long-term prognosis depends on the severity of the liver disease, which is partly dependent on the mutation present.2 Other ichthyoses with neonatal cholestasis include arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome, type 2 Gaucher’s disease, and MEDNIK syndrome (mental retardation, enteropathy, deafness, neuropathy, ichthyosis and keratodermia).3

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The Genetic Drivers of Juvenile, Young, and Early-Onset Parkinson’s Disease in India

Movement Disorders, Nov 28, 2023

Recent studies have advanced our understanding of the genetic drivers of Parkinson's disease (PD). Rare variants in more than 20 genes are considered causal for PD, and the latest PD genome-wide association study (GWAS) identified 90 independent risk loci. However, there remains a gap in our understanding of PD genetics outside of the European populations in which the vast majority of these studies were focused.

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Clinical Utility of Proband Only Clinical Exome Sequencing in Neurodevelopmental Disorders

Indian J Pediatr, Nov 9, 2023

PMID: 37943464

Chromosomal microarray is recommended as the first line of investigation in neurodevelopmental disorders (NDDs). However, advances in next-generation sequencing have unraveled more than 900 genes associated with NDDs, thus improving the genetic diagnosis. Therefore, this study was conducted to explore the utility of clinical exome sequencing (CES) in NDDs from a tertiary care centre in India.

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Kindler syndrome with a novel mutation and a rare gynaecological complication

Clinical and Experimental Dermatology, llad364, 2023

PMID: 37878805

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Identification of a shared, common haplotype segregating with an SGCB c.544 T > G mutation in Indian patients affected with sarcoglycanopathy

Nature Scientific reports, Vol. 13, Issue 1, Pages 15095, 2023

PMID: 37699968

Sarcoglycanopathy is the most frequent form of autosomal recessive limb- girdle muscular dystrophies caused by mutations in SGCB gene encoding beta-sarcoglycan proteins. In this study, we describe a shared, common haplotype co-segregating in 14 sarcoglycanopathy cases from 13 unrelated families from south Indian region with the likely pathogenic homozygous mutation c.544 T > G (p.Thr182Pro) in SGCB.

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Intervention of next-generation sequencing in diagnosis of Alzheimer’s disease: challenges and future prospects

Dementia & neuropsychologia, Vol. 17, Pages e20220025, 2023

PMID: 37577182

Clinical diagnosis of several neurodegenerative disorders based on clinical phenotype is challenging due to its heterogeneous nature and overlapping disease manifestations. Therefore, the identification of underlying genetic mechanisms is of paramount importance for better diagnosis and therapeutic regimens.

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Novel homozygous leptin receptor mutation in an infant with monogenic obesity

Pediatric endocrinology, diabetes, and metabolism, Vol. 29, Issue 2, Pages 118-123, 2023

PMID: 37728464

Monogenic obesity can be caused by a mutation in one of the single genes involved in hunger and satiety. The most common mutations affect melanocortin 4 (MC4) followed by the leptin gene and its receptor. Leptin receptor (LEPR) gene mutation is an extremely rare endocrine disease characterized by early-onset obesity, hyperphagia in addition to pituitary hormone deficiency, and metabolic abnormalities.

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South Asian Medical Cohorts Reveal Strong Founder Effects And High Rates Of Homozygosity

Nature communications, Vol. 14, Issue 1, Pages 3377, 2023

PMID: 37291107

The benefits of large-scale genetic studies for healthcare of the populations studied are well documented, but these genetic studies have traditionally ignored people from some parts of the world, such as South Asia. Here we describe whole genome sequence (WGS) data from 4806 individuals recruited from the healthcare delivery systems of Pakistan, India and Bangladesh, combined with WGS from 927 individuals from isolated South Asian populations.

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Filaggrin gene polymorphisms in Indian children with atopic dermatitis: A cross-sectional multicentre study

Indian journal of dermatology, venereology and leprology, Pages 1-9, 2023

PMID: 37067103

Filaggrin (FLG) gene encoding the protein filaggrin plays an important role in barrier function of the skin and its alteration is a predisposing factor for atopic dermatitis. FLG gene variants result in absent or decreased filaggrin protein. Worldwide, the prevalence of FLG variants ranges from 14 to 56%. FLG null variants are distinct in each population.

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Comprehensive laboratory diagnosis of Fanconi anaemia: comparison of cellular and molecular analysis

Journal of medical genetics, Vol. 60, Issue 8, Pages 801-809, 2023

PMID: 36894310

Fanconi anaemia (FA) is a rare inherited bone marrow failure disease caused by germline pathogenic variants in any of the 22 genes involved in the FA-DNA interstrand crosslink (ICL) repair pathway. Accurate laboratory investigations are required for FA diagnosis for the clinical management of the patients. We performed chromosome breakage analysis (CBA), FANCD2 ubiquitination (FANCD2-Ub) analysis and exome sequencing of 142 Indian patients with FA and evaluated the efficiencies of these methods in FA diagnosis.

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True Fetal Trisomy 22 Detected Using Genome-Wide Noninvasive Prenatal Testing

Journal of obstetrics and gynaecology of India, Vol. 73, Issue 2, Pages 180-182, 2023

PMID: 37073230

Autosomal aneuploidies occurring in chromosomes other than 13, 18, and 21 and sex chromosomal aneuploidies are referred to as 'Rare autosomal aneuploidies' (RAAs). A prenatal incidence of 0.41% is noted for RAAs on chorionic villus sampling (CVS) procedures. Aneuploidies in autosomes other than 13, 18, and 21 and sex chromosomal aneuploidies may result in increased fetal-placental diseases such as non-viable pregnancy, early miscarriage, intrauterine fetal growth restriction, uniparental disomy, multiple congenital anomalies, fetal demise, or normal live birth [1].

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Genotype-phenotype correlation and natural history study of dysferlinopathy: a single-centre experience from India

Neurogenetics, Vol. 24, Issue 1, Pages 43-53, 2022

PMID: 36580222

Dysferlinopathies are a group of limb-girdle muscular dystrophies causing significant disability in the young population. There is a need for studies on large cohorts to describe the clinical, genotypic and natural history in our subcontinent. To describe and correlate the clinical, genetic profile and natural history of genetically confirmed dysferlinopathies.

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Near-chromosomal de novo assembly of Bengal tiger genome reveals genetic hallmarks of apex predation

GigaScience, Vol. 12, 2022

PMID: 36576130

The tiger, a poster child for conservation, remains an endangered apex predator. Continued survival and recovery will require a comprehensive understanding of genetic diversity and the use of such information for population management. A high-quality tiger genome assembly will be an important tool for conservation genetics, especially for the Indian tiger, the most abundant subspecies in the wild.

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Metabolic and Genetic Evaluation in Children with Nephrolithiasis

Indian journal of pediatrics, Vol. 89, Issue 12, Pages 1243-1250, 2022

PMID: 35819704

To evaluate metabolic and genetic abnormalities in children with nephrolithiasis attending a referral center in North India.

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A novel compound heterozygous BEST1 gene mutation in two siblings causing autosomal recessive bestrophinopathy

BMC ophthalmology, Vol. 22, Issue 1, Pages 493, 2022

PMID: 36527004

To describe the clinical features, imaging characteristics, and genetic test results associated with a novel compound heterozygous mutation of the BEST1 gene in two siblings with autosomal recessive bestrophinopathy.

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Genome-Wide Polygenic Score Predicts Large Number of High Risk Individuals in Monogenic Undiagnosed Young Onset Parkinson’s Disease Patients from India

Advanced biology, Vol. 6, Issue 11, Pages e2101326, 2022

PMID: 35810474

Parkinson's disease (PD) is a genetically heterogeneous neurodegenerative disease with poorly defined environmental influences. Genomic studies of PD patients have identified disease-relevant monogenic genes, rare variants of significance, and polygenic risk-associated variants.

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Molecular epidemiology of SARS-CoV-2 in healthcare workers and identification of viral genomic correlates of transmissibility and vaccine break through infection: A retrospective observational study from a cancer hospital in eastern India

Indian journal of medical microbiology, Vol. 41, Pages 104-110, 2022

PMID: 36244851

Despite COVID vaccination with ChAdOx1 ncov-19 (COVISHIELD(R)) (ChAdOx1 ncov-19) a large number of healthcare workers (HCWs) were getting infected in wave-2 of the pandemic in a cancer hospital of India. It was important therefore to determine the genotypes responsible for vaccine breakthrough infections.

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Think of SCA45 in Late-Onset Familial Ataxias: The First Report from the Indian Subcontinent with a Novel Variant

Movement disorders clinical practice, Vol. 9, Issue 8, Pages 1140-1143, 2022

PMID: 36339299

An 82-year-old male patient presented with insidious onset and slowly progressive imbalance during walking over a period of the last 20 years. He also suffered from recurrent bouts of bullous pemphigoid for the last 30 years and developed hearing difficulty for the last 3 years. He had a strong family history of late onset gait imbalance involving his mother, four of his elder brothers, and two of their daughters (Fig. 1).

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Multiomic analysis of papillary thyroid cancers identifies BAIAP2L1-BRAF fusion and requirement of TRIM25, PDE5A and PKCdelta for tumorigenesis

Molecular cancer, Vol. 21, Issue 1, Pages 195, 2022

PMID: 36217175

Papillary thyroid carcinoma (PTC) is one of the most common forms of thyroid cancer with a cure rate of over 90% after surgery. However, aggressive forms may still occur, and personalized therapeutic strategies are increasingly required.

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Bioplatforms in liquid biopsy: advances in the techniques for isolation, characterization and clinical applications

Biotechnology & genetic engineering reviews, Vol. 38, Issue 2, Pages 339-383, 2022

PMID: 35968863

Tissue biopsy analysis has conventionally been the gold standard for cancer prognosis, diagnosis and prediction of responses/resistances to treatments. The existing biopsy procedures used in clinical practice are, however, invasive, painful and often associated with pitfalls like poor recovery of tumor cells and infeasibility for repetition in single patients.

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Wilson Disease: Never Too Late . .

The American journal of medicine, Vol. 135, Issue 9, Pages e370-e371, 2022

PMID: 35580721

A 43-year-old man presented with a 4-month history of abdominal bloating, loss of appetite and 5 kg weight loss. He was previously fit and well, with no history of alcohol or drug ingestion, and no prior blood transfusion. Clinical examination revealed pigmentation around the cornea of both eyes, consistent with Kayser-Fleischer (KF) rings (Figure A), but there were no other clinical features of chronic liver disease.

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Genomic Variations in ATP7B Gene in Indian Patients with Wilson Disease

Indian journal of pediatrics, Vol. 90, Issue 3, Pages 240-248, 2022

PMID: 36112267

To report genotype data of the patients with Wilson disease (WD) hailing from across several parts of India to add to the available spectrum of causative variants in ATP7B gene (ATPase copper transporting beta polypeptide gene) and associated phenotypes in the Indian population.

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Selected commensals educate the intestinal vascular and immune system for immunocompetence

Microbiome, Vol. 10, Issue 1, Pages 158, 2022

PMID: 36171625

The intestinal microbiota fundamentally guides the development of a normal intestinal physiology, the education, and functioning of the mucosal immune system. The Citrobacter rodentium-carrier model in germ-free (GF) mice is suitable to study the influence of selected microbes on an otherwise blunted immune response in the absence of intestinal commensals. Here, we describe that colonization of adult carrier mice with 14 selected commensal microbes (OMM12 + MC2) was sufficient to reestablish the host immune response to enteric pathogens; this conversion was facilitated by maturation and activation of the intestinal blood vessel system and the step- and timewise stimulation of innate and adaptive immunity.

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Detection of IEMs by Mass Spectrometry Techniques in High-Risk Children: A Pilot Study

Indian journal of pediatrics, Vol. 89, Issue 9, Pages 885-893, 2022

PMID: 35713767

To determine the incidence and types of inborn errors of metabolism (IEMs) in high-risk children using mass spectrometry techniques.

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Spectrum and management of breast cancer patients with variant of uncertain significance mutations at a tertiary care centre in North India

Ecancermedicalscience, Vol. 16, Pages 1434, 2022

PMID: 36200007

The spectrum and significance of Variants of Uncertain Significance (VUS) mutations in breast cancer predisposition genes is poorly defined in the Indian population.

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Whole-exome sequencing and variant spectrum in children with suspected inherited renal tubular disorder: the East India Tubulopathy Gene Study

Pediatric nephrology (Berlin, Germany), Vol. 37, Issue 8, Pages 1811-1836, 2022

PMID: 35006361

Inherited tubulopathies are a heterogeneous group of genetic disorders making whole-exome sequencing (WES) the preferred diagnostic methodology.

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Genetic Variation in Reproductive Investment Across an Ephemerality Gradient in Daphnia pulex

Molecular biology and evolution, Vol. 39, Issue 6, 2022

PMID: 35642301

Species across the tree of life can switch between asexual and sexual reproduction. In facultatively sexual species, the ability to switch between reproductive modes is often environmentally dependent and subject to local adaptation. However, the ecological and evolutionary factors that influence the maintenance and turnover of polymorphism associated with facultative sex remain unclear. We studied the ecological and evolutionary dynamics of reproductive investment in the facultatively sexual model species, Daphnia pulex.

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Clinical, radiological and molecular studies in 24 individuals with Dyggve-Melchior-Clausen dysplasia and Smith-McCort dysplasia from India

Journal of medical genetics, Vol. 60, Issue 2, Pages 204-211, 2022

PMID: 35477554

Dyggve-Melchior-Clausen dysplasia (DMC) and Smith-McCort dysplasia (SMC types 1 and 2) are rare spondyloepimetaphyseal dysplasias with identical radiological findings. The presence of intellectual disability in DMC and normal intellect in SMC differentiates the two. DMC and SMC1 are allelic and caused by homozygous or compound heterozygous variants in DYM. SMC2 is caused by variations in RAB33B. Both DYM and RAB33B are important in intravesicular transport and function in the Golgi apparatus.

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Oculogyric Crisis Phenotype of Levodopa-Induced Ocular Dyskinesia

Movement disorders clinical practice, Vol. 9, Issue 3, Pages 390-393, 2022

PMID: 36989007

Ocular dyskinesia (OD) is an uncommon form of the levodopa induced dyskinesia (LIOD) characterized by short‐lasting horizontal or upward conjugate gaze deviation. More sustained deviations resembling oculogyric crises (OGC) are distinctly uncommon. 1 , 2 , 3 , 4

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Clinical, genetic profile and disease progression of sarcoglycanopathies in a large cohort from India: high prevalence of SGCB c.544A > C

Neurogenetics, Vol. 23, Issue 3, Pages 187-202, 2022

PMID: 35416532

The clinico-genetic architecture of sarcoglycanopathies in Indian patients is reported only as short series. In the present study, we aimed to investigate the clinical picture, genetic basis, and disease progression of patients genetically confirmed to have sarcoglycanopathy. Next-generation sequencing was performed in 68 probands with suspected sarcoglycanopathy.

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Positive selection over the mitochondrial genome and its role in the diversification of gentoo penguins in response to adaptation in isolation

Nature Scientific Reports volume 12, Article number: 3767, 2022

PMID: 35260629

Our study suggests that local adaptation of gentoo penguins has emerged as a response to environmental variability promoting the fixation of mitochondrial haplotypes in a non-random manner. Mitogenome adaptation is thus likely to have been associated with gentoo penguin diversification across the Southern Ocean and to have promoted their survival in extreme environments such as Antarctica. Such selective processes on the mitochondrial genome may also be responsible for the discordance detected between nuclear- and mitochondrial-based phylogenies of gentoo penguin lineages.

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Evaluation of cytogenetic and molecular markers with MTX-mediated toxicity in pediatric acute lymphoblastic leukemia patients

Cancer chemotherapy and pharmacology, Vol. 89, Issue 3, Pages 393-400, 2022

PMID: 35157101

Pediatric acute lymphoblastic leukemia (pALL) patients have better overall survival and methotrexate (MTX) is an effective drug used in their treatment. However, the treatment-related adverse effects (TRAEs) have a bigger impact on the therapy. In this study, we have evaluated the association of polymorphisms in genes encoding proteins engaged in MTX metabolism, and the cytogenetic aberrations with TRAEs.

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Drug-resistant ‘Non-Lesional’ Visual Sensitive Epilepsies of Childhood – Electroclinical Phenotype-Genotype Associations

Neurology India, Vol. 69, Issue 6, Pages 1701-1705, 2021

PMID: 34979672

Sporadic nonlesional intractable visual-sensitive epilepsies of childhood represent a challenging subset of epilepsies in terms of management and prognostication given a propensity to evolve as epileptic encephalopathy.

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Novel Consensus Splice Site Pathogenic Variation in THOC2 Gene Leads to Recurrent Arthrogryposis Multiplex Congenita Phenotype: A Case Report

Cureus, Vol. 13, Issue 11, Pages e19682, 2021

PMID: 34976470

The THOC2 gene encodes THO complex subunit 2, a subunit of the Transcription-Export (TREX) complex which binds specifically to splice messenger ribonucleic acid (mRNAs) to facilitate mRNA export. Mutations in the THOC2 gene have been described to lead to X-linked mental retardation syndrome type 12/35 (XLMR-12/35) (MIM#300957). Here, we describe for the first time a recurrent arthrogryposis multiplex congenita phenotype (AMC) in two male fetuses in a family.

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Phenotypic expression and clinical outcomes in a South Asian PRKAG2 cardiomyopathy cohort

Nature Scientific reports, Vol. 10, Issue 1, Pages 20610, 2020

PMID: 33244021

The PRKAG2 syndrome is a rare autosomal dominant phenocopy of sarcomeric hypertrophic cardiomyopathy (HCM), characterized by ventricular pre- excitation, progressive conduction system disease and left ventricular hypertrophy. This study describes the phenotype, genotype and clinical outcomes of a South-Asian PRKAG2 cardiomyopathy cohort over a 7-year period.

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Growth and neurodevelopmental disorder with arthrogryposis, microcephaly and structural brain anomalies caused by Bi-allelic partial deletion of SMPD4 gene

Journal of human genetics, Vol. 67, Issue 3, Pages 133-136, 2021

PMID: 34621002

Neutral sphingomyelinases have an important role in generation of ceramide and phosphorylcholine from sphingomyelins which then act as secondary messengers in various signaling pathways of the cellular machinery. They function ubiquitously with a predominant role in the central nervous system.

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Profile of Pathogenic Mutations and Evaluation of Germline Genetic Testing Criteria in Consecutive Breast Cancer Patients Treated at a North Indian Tertiary Care Center

Annals of surgical oncology, Vol. 29, Issue 2, Pages 1423-1432, 2021

PMID: 34601666

The burden of hereditary breast cancer in India is not well defined. Moreover, genetic testing criteria (National Comprehensive Cancer Network [NCCN] and Mainstreaming Cancer Genetics [MCG] Plus) have never been validated in the Indian population.

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Initial experience and results of a cardiogenetic clinic in a tertiary cardiac care center in India

Annals of pediatric cardiology, Vol. 14, Issue 3, Pages 443-448, 2021

PMID: 34667425

Cardiogenetic clinics have gained importance over the past two decades due to their ability to integrate genetic medicine with clinical cardiology and thereby provide comprehensive care to affected patients and their families.[1,2] A multidisciplinary team approach comprising the cardiologist, electrophysiologist, and clinical geneticist has resulted in significant changes in the management of children with inherited cardiac disorder

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Spinocerebellar Ataxia 28 Presenting as Predominantly Generalized Dystonia

Annals of Indian Academy of Neurology, Vol. 24, Issue 5, Pages 832-834, 2021

PMID: 35002173

Spinocerebellar ataxia type 28 (SCA 28) is characterized by young-adult onset slowly progressive gait and limb ataxia, dysarthria, ptosis, and Opthalmoplegia. We report a case of SCA 28 in a 37-year-old gentleman with predominant dystonia, bilateral optic atrophy, and cerebellar ataxia.

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Maternal opioid use disorder: Placental transcriptome analysis for neonatal opioid withdrawal syndrome

Genomics, Vol. 113, Issue 6, Pages 3610-3617, 2021

PMID: 34352367

Excessive prenatal opioid exposure may lead to the development of Neonatal Opioid Withdrawal Syndrome (NOWS). RNA-seq was done on 64 formalin-fixed paraffin-embedded placental tissue samples from 32 mothers with opioid use disorder, with newborns with NOWS that required treatment, and 32 prenatally unexposed controls.

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Retinoblastoma genetics screening and clinical management

BMC medical genomics, Vol. 14, Issue 1, Pages 188, 2021

PMID: 34294096

India accounts for 20% of the global retinoblastoma (RB) burden. However, the existing data on RB1 gene germline mutations and its influence on clinical decisions is minimally explored.

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Nemaline Rod/Cap Myopathy Due to Novel Homozygous MYPN Mutations: The First Report from South Asia and Comprehensive Literature Review

Journal of clinical neurology (Seoul, Korea), Vol. 17, Issue 3, Pages 409-418, 2021

PMID: 34184449

Pathogenic variants in the myopalladin gene (MYPN) are known to cause mildly progressive nemaline/cap myopathy. Only nine cases have been reported in the English literature.

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Wilms tumor with Mulibrey Nanism: A case report and review of literature

Cancer reports (Hoboken, N.J.), Vol. 5, Issue 5, Pages e1512, 2021

PMID: 34309235

Mulibrey-Nanism (Muscle-liver-brain-eye Nanism = dwarfism; MUL) is a rare genetic syndrome. The underlying TRIM37 mutation predisposes these children to develop tumors frequently. In the largest published series of MUL, 8% patients were reported to develop Wilms tumor (WT).

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HopA1 Effector from Pseudomonas syringae pv syringae Strain 61 Affects NMD Processes and Elicits Effector-Triggered Immunity

International journal of molecular sciences, Vol. 22, Issue 14, Pages 7440, 2021

PMID: 34299060

Pseudomonas syringae-secreted HopA1 effectors are important determinants in host range expansion and increased pathogenicity. Their recent acquisitions via horizontal gene transfer in several non-pathogenic Pseudomonas strains worldwide have caused alarming increase in their virulence capabilities.

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Insulin Infusion Is Linked to Increased NPPC Expression in Muscle and Plasma C-type Natriuretic Peptide in Male Dogs

Journal of the Endocrine Society, Vol. 5, Issue 7, Pages bvab088, 2021

PMID: 34131611

The purpose of this study was to assess insulin-stimulated gene expression in canine skeletal muscle with a particular focus on NPPC, the gene that encodes C-type natriuretic peptide, a key hormonal regulator of cardiometabolic function. Four conscious canines underwent hyperinsulinemic, euglycemic clamp studies.

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Myoneuropathic presentation of limb girdle muscular dystrophy R8 with a novel TRIM32 mutation

Neuromuscular disorders : NMD, Vol. 31, Issue 9, Pages 886-890, 2021

PMID: 34244021

TRIM 32-related Limb Girdle Muscular Dystrophy (LGMD R8/2H) is a rare genetic muscle disease reported in fewer than 100 patients worldwide. Here, we report a male patient with progressive proximo-distal lower limb weakness with onset in the third decade who had mixed myopathic and neurogenic pattern in electrophysiology and muscle biopsy. Clinical exome sequencing revealed a homozygous pathogenic single base pair insertion in exon 2 of the TRIM32 gene confirming the diagnosis of LGMD R8. This is a novel frameshift mutation and one of the very few cases of LGMD R8 reported from India.

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Immunodominant T-cell epitopes from the SARS-CoV-2 spike antigen reveal robust pre-existing T-cell immunity in unexposed individuals

Nature Scientific reports, Vol. 11, Issue 1, Pages 13164, 2021

PMID: 34162945

The COVID-19 pandemic has revealed a range of disease phenotypes in infected patients with asymptomatic, mild, or severe clinical outcomes, but the mechanisms that determine such variable outcomes remain unresolved. In this study, we identified immunodominant CD8 T-cell epitopes in the spike antigen using a novel TCR-binding algorithm.

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Chorea-acanthocytosis: 3 New Families with Novel Genetic and Metabolic Findings

Annals of Indian Academy of Neurology, Vol. 24, Issue 3, Pages 452-456, 2021

PMID: 34447025

Neuroacanthocytosis syndromes are a group of rare heterogeneous neurological disorders characterized by the presence of acanthocytes in peripheral blood smear and basal ganglia degeneration.[1]

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Recent Evolutionary History of Tigers Highlights Contrasting Roles of Genetic Drift and Selection

Molecular biology and evolution, Vol. 38, Issue 6, Pages 2366-2379, 2021

PMID: 33592092

Species conservation can be improved by knowledge of evolutionary and genetic history. Tigers are among the most charismatic of endangered species and garner significant conservation attention. However, their evolutionary history and genomic variation remain poorly known, especially for Indian tigers.

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Matrilineal analysis of mutations in the DMD gene in a multigenerational South Indian cohort using DMD gene panel sequencing

Molecular genetics & genomic medicine, Vol. 9, Issue 5, Pages e1633, 2021

PMID: 33960727

Duchenne muscular dystrophy (DMD) is an X-linked recessive neuromuscular disorder characterised by progressive irreversible muscle weakness, primarily of the skeletal and the cardiac muscles. DMD is characterised by mutations in the dystrophin gene, resulting in the absence or sparse quantities of dystrophin protein. A precise and timely molecular detection of DMD mutations encourages interventions such as carrier genetic counselling and in undertaking therapeutic measures for the DMD patients.

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A New Variant of an Old Itch: Novel Missense Variant in ABCB4 Presenting with Intractable Pruritus

Journal of clinical and experimental hepatology, Vol. 12, Issue 2, Pages 701-704, 2021

PMID: 35535055

We report a novel homozygous missense variant in ABCB4 gene in a Yemeni child born to consanguineous parents, with a significant family history of liver disease-related deaths, resulting in a progressive familial intrahepatic cholestasis (PFIC) type 3 phenotype requiring liver transplantation for intractable pruritus.

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Pharmacogenetic evaluation of 6-mercaptopurine-mediated toxicity in pediatric acute lymphoblastic leukemia patients from a South Indian population

Pharmacogenomics, Vol. 22, Issue 7, Pages 401-411, 2021

PMID: 33876659

To evaluate the variants in the genes coding for the proteins involved in thiopurine and folate metabolism with treatment related adverse effects (TRAEs).

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Human ACE2 receptor polymorphisms predict SARS-CoV-2 susceptibility

bioRxiv,2020.04.07.024752, 2021

In this study, we assessed if ACE2 polymorphisms might alter host susceptibility to SARS-CoV-2 by affecting the ACE2 S-protein interaction. Our comprehensive analysis of several large genomic datasets that included over 290,000 samples representing >400 population groups identified multiple ACE2 protein-altering variants, some of which mapped to the S-protein-interacting ACE2 surface.

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Whole-exome sequencing identifies two novel ALMS1 mutations in Indian patients with Leber congenital amaurosis

Human genome variation, Vol. 8, Issue 1, Pages 12, 2021

PMID: 33782391

Leber congenital amaurosis (LCA) is a severe autosomal recessive retinal degenerative disease. The current study describes exome sequencing results for two unrelated Indian LCA patients carrying novel nonsense p.(Glu636*) and frameshift p.(Pro2281Leufs*63) mutations in the ALMS1 gene. Although ALMS1 gene mutations are associated with Alstrom syndrome (AS), the current patients did not exhibit typical syndromic features of AS. These data suggest that ALMS1 should be included in the candidate gene panel for LCA to improve diagnostic efficiency.

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The Spectrum of Clinical, Immunological, and Molecular Findings in Five Patients with Major Histocompatibility Complex Class II Deficiency from India

Frontiers in immunology, Vol. 9, Pages 188, 2021

PMID: 33746956

Major histocompatibility complex (MHC) class II deficiency is a rare autosomal recessive form of primary immunodeficiency disorder (PID) characterized by the deficiency of MHC class II molecules. This deficiency affects the cellular and humoral immune response by impairing the development of CD4(+) T helper (Th) cells and Th cell-dependent antibody production by B cells.

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A Young Girl With Bronchiectasis and Elevated Sweat Chloride

Chest, Vol. 159, Issue 3, Pages e155-e158, 2021

PMID: 33678284

CASE PRESENTATION: A 14-year old girl presented with history of productive cough since the age of 3 years. For the past 6 years, she complained of chest tightness and wheezing. There was also nasal stuffiness and discharge for the past 6 years. She denied history of hemoptysis, ear discharge, or chest pain. There was no history of respiratory distress at the time of birth. Her brother also suffered from productive cough and wheezing since the age of 3 years. However, both her parents were asymptomatic.

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Clinical Study of 668 Indian Subjects with Juvenile, Young, and Early Onset Parkinson’s Disease

The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques, Vol. 49, Issue 1, Pages 93-101, 2021

PMID: 33685545

To determine the demographic pattern of juvenile-onset parkinsonism (JP, <20 years), young-onset (YOPD, 20-40 years), and early onset (EOPD, 40-50 years) Parkinson's disease (PD) in India.

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The Spectrum of Clinical, Immunological, and Molecular Findings in Familial Hemophagocytic Lymphohistiocytosis: Experience From India

Frontiers in immunology, Vol. 12, Pages 612583, 2021

PMID: 33746956

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of immune dysregulation characterized by hyperactivation of the immune system, excessive cytokine secretion and severe systemic inflammation. HLH is classified as familial (FHL) when associated with mutations in PRF1, UNC13D, STX11, and STXBP2 genes.

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Novel CTSF Indel in a patient with Kufs disease and resistant schizophrenia: A case report

Schizophrenia research, Vol. 228, Pages 435-437, 2021

PMID: 33578366

Neuronal Ceroid Lipofuscinoses (NCL) are lysosomal storage disorders manifesting as progressive encephalopathies. Kufs disease is a type of adult NCL caused by mutations in the cathepsin F (CTSF) gene (Smith et al., 2013).

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BCR-ABL1 kinase domain mutation analysis by next generation sequencing detected additional mutations in chronic myeloid leukemia patients with suboptimal response to imatinib

Leukemia & lymphoma, Vol. 62, Issue 6, Pages 1528-1531, 2021

PMID: 33478278

Mutations in the BCR-ABL1 kinase domain (BCR-ABL1 KD) is one of the most common determinants of tyrosine kinase inhibitor (TKI) resistance in patients with chronic myelogenous leukemia (CML) [1].

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Genetic Testing in Neonatal Intensive Care: Experience from a Tertiary Care Unit

Indian journal of pediatrics, Vol. 88, Issue 4, Pages 398-399, 2021

PMID: 33403610

Families of infants with malformations and atypical chronic illnesses face physical, emotional, social, and financial turmoil [1]. Several investigations are conducted on these neonates, not always yielding clear diagnosis [2].

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Prenatal Diagnosis for Primary Immunodeficiency Disorders-An Overview of the Indian Scenario

Frontiers in immunology, Vol. 11, Pages 612316, 2020

PMID: 33365035

Prenatal Diagnosis (PND) forms an important part of primary preventive management for families having a child affected with primary immunodeficiency. Although individually sparse, collectively this group of genetic disorders represents a significant burden of disease.

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Multi-Omics Analysis to Characterize Cigarette Smoke Induced Molecular Alterations in Esophageal Cells

Frontiers in oncology, Vol. 10, Pages 1666, 2020

PMID: 33251127

Though smoking remains one of the established risk factors of esophageal squamous cell carcinoma, there is limited data on molecular alterations associated with cigarette smoke exposure in esophageal cells. To investigate molecular alterations associated with chronic exposure to cigarette smoke, non-neoplastic human esophageal epithelial cells were treated with cigarette smoke condensate (CSC) for up to 8 months.

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Reply to: Fatal Familial Insomnia: A Rare Disease with Unique Clinico- Neurophysiological Features

Movement disorders clinical practice, Vol. 8, Issue 1, Pages 164-165, 2020

PMID: 33426176

Baldelli et al. 1 raise an important issue in respect to our report of a 54 year old man with D178N mutation in PRNP gene presenting with rapidly progressive autosomal dominant ataxia and vocal cord palsy.

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Ophthatome: an integrated knowledgebase of ophthalmic diseases for translating vision research into the clinic

BMC ophthalmology, Vol. 20, Issue 1, Pages 442, 2020

PMID: 33172432

Medical big data analytics has revolutionized the human healthcare system by introducing processes that facilitate rationale clinical decision making, predictive or prognostic modelling of the disease progression and management, disease surveillance, overall impact on public health and research. Although, the electronic medical records (EMR) system is the digital storehouse of rich medical data of a large patient cohort collected over many years, the data lack sufficient structure to be of clinical value for applying deep learning methods and advanced analytics to improve disease management at an individual patient level or for the discipline in general. Ophthatome captures data contained in retrospective electronic medical records between September 2012 and January 2018 to facilitate translational vision research through a knowledgebase of ophthalmic diseases.

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Clinico-epidemiological and genomic profile of first Zika Virus outbreak in India at Jaipur city of Rajasthan state

Journal of infection and public health, Vol. 13, Issue 12, Pages 1920-1926, 2020

PMID: 33172818

First Zika virus (ZIKV) positive case from North India was detected on routine surveillance of Dengue-Like Illness in an 85-year old female. Objective of the study was to conduct an investigation for epidemiological, clinical and genomic analysis of first ZIKV outbreak in Rajasthan, North India and enhance routine ZIKV surveillance.

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NGS-based expanded carrier screening for genetic disorders in North Indian population reveals unexpected results – a pilot study

BMC medical genetics, Vol. 21, Issue 1, Pages 216, 2020

PMID: 33138774

To determine the carrier frequency and pathogenic variants of common genetic disorders in the north Indian population by using next generation sequencing (NGS).

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Infantile spasms: Etiology, lead time and treatment response in a resource limited setting

Epilepsy & behavior reports, Vol. 14, Pages 100397, 2020

PMID: 33196034

This study explores the etiology and lead time to treatment for infantile spasm (IS) patients and their effect on treatment responsiveness, in a limited resource setting. Patients with IS onset age ≤12 months', seen over 3 years were recruited retrospectively.

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Seven novel genetic variants in a North Indian cohort with classical homocystinuria

Nature Scientific reports, Vol. 10, Issue 1, Pages 17299, 2020

PMID: 33057012

Classical homocystinuria is the most common cause of isolated homocystinuria. The variants of the CBS gene remain unidentified in Indian children with this disorder. Based on the hallmark clinical features, family history, and/or biochemical clues for classical homocystinuria, 16 children below the age of 18 years were evaluated by Sanger sequencing of the coding exons of CBS gene with flanking intronic regions.

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Phenotypic variability in distal acidification defects associated with WDR72 mutations

Pediatric nephrology (Berlin, Germany), Vol. 36, Issue 4, Pages 881-887, 2020

PMID: 33033857

Distal renal tubular acidosis (RTA) is typically caused by defects in ATP6V0A4, ATP6V1B1, and SLC4A1, accounting for 60-80% of patients. Genes recently implicated include FOXI1, ATP6V1C2, and WDR72, of which WDR72 is associated with dental enamel defects.

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Genotype-phenotype correlates of infantile-onset developmental & epileptic encephalopathy syndromes in South India: A single centre experience

Epilepsy Res, Vol.166, Pages 106398, 2020

PMID: 32593896

A paucity of literature exists on genotype- phenotype correlates of 'unknown-etiology' infantile-onset developmental-epileptic encephalopathies (DEE) from India. The primary objective was to explore the yield of genetic testing in identifying potential disease causing variants in electro-clinical phenotypes of DEE. An observational hospital-based study was undertaken on children with unexplained refractory seizure-onset ≤12 months age and developmental delay, whose families consented and underwent genetic testing during a three year time period (2016-2018) by next-generation sequencing (NGS) or multiplex ligand protein amplification.

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Integrated genomic analysis reveals mutated ELF3 as a potential gallbladder cancer vaccine candidate

Nature communications, Vol. 11, Issue 1, Pages 4225, 2020

PMID: 32839463

Gallbladder cancer (GBC) is an aggressive gastrointestinal malignancy with no approved targeted therapy. Here, we analyze exomes (n = 160), transcriptomes (n = 115), and low pass whole genomes (n = 146) from 167 gallbladder cancers (GBCs) from patients in Korea, India and Chile.

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Mutational Landscape of Esophageal Squamous Cell Carcinoma in an Indian Cohort

Frontiers in oncology, Vol. 10, Pages 1457, 2020

PMID: 32974170

Esophageal squamous cell carcinoma (ESCC) is the most common histological subtype of esophageal cancer in India. Cigarette smoking and chewing tobacco are known risk factors associated with ESCC. However, genomic alterations associated with ESCC in India are not well-characterized.

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A Case of Autosomal Dominant Ataxia with Vocal Cord Palsy Attributed to a Mutation in the PRNP Gene

Movement disorders clinical practice, Vol. 7, Issue 6, Pages 688-692, 2020

PMID: 32775516

Cerebellar ataxias, are a group progressively expanding spectrum of heterogeneous disorders. The clinical features and life expectancies are varied based on genetic and phenotypic presentations. 1 We present a familial case with an autosomal dominant inheritance of rapidly progressive ataxia with vocal cord palsy, due to D178N mutation in the PRNP gene.

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Genome-wide analyses reveal drivers of penguin diversification

PNAS, 117 (36) 22303-22310, 2020

PMID: 32817535

Penguins are the only extant family of flightless diving birds. They currently comprise at least 18 species, distributed from polar to tropical environments in the Southern Hemisphere. The history of their diversification and adaptation to these diverse environments remains controversial. We used 22 new genomes from 18 penguin species to reconstruct the order, timing, and location of their diversification, to track changes in their thermal niches through time, and to test for associated adaptation across the genome.

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Validation of a Genome-Wide Polygenic Score for Coronary Artery Disease in South Asians

Journal of the American College of Cardiology, Vol. 76, Issue 6, Pages 703-714, 2020

PMID: 32762905

Genome-wide polygenic scores (GPS) integrate information from many common DNA variants into a single number. Because rates of coronary artery disease (CAD) are substantially higher among South Asians, a GPS to identify high-risk individuals may be particularly useful in this population.

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Naja naja (Indian Cobra)

Trends in genetics : TIG, Vol. 36, Issue 10, Pages 804-806, 2020

PMID: 32768150

The Indian cobra genome comprises 38 chromosomes (2n) totaling 1.79 Gb with a GC content of ~40% and repeat content of 43%. The near-chromosomal assembly is highly contiguous with 95% of the genome represented by 19 large scaffolds that correspond to its chromosomes. The largest scaffold at ~375 Mb spans the entire chromosome 1. The genome codes for 23 248 predicted proteins and includes 139 venom toxins that target multiple physiological processes (Figure 1).

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Transcriptomic profile of adverse neurodevelopmental outcomes after neonatal encephalopathy

Nature Genetics, Sci Rep 10, 13100, 2020

PMID: 32753750

A rapid and early diagnostic test to identify the encephalopathic babies at risk of adverse outcome may accelerate the development of neuroprotectants. We examined if a whole blood transcriptomic signature measured soon after birth, predicts adverse neurodevelopmental outcome eighteen months after neonatal encephalopathy. We performed next generation sequencing on whole blood ribonucleic acid obtained within six hours of birth from the first 47 encephalopathic babies recruited to the Hypothermia for Encephalopathy in Low and middle-income countries (HELIX) trial.

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Next-Generation Sequencing in a Cohort of Asian Indian Patients with the Duchenne Muscular Dystrophy Phenotype: Diagnostic Yield and Mutation Spectrum

Journal of pediatric genetics, Vol. 10, Issue 1, Pages 23-28, 2020

PMID: 33552634

Multiplex ligation-dependent probe amplification (MLPA) detects exonic deletions and duplications in the DMD gene in around 65 to 70% of patients with the Duchenne muscular dystrophy (DMD) phenotype. This study looks at the diagnostic yield of next-generation sequencing (NGS) and the mutation spectrum in an Asian Indian cohort of MLPA-negative cases with the DMD phenotype. NGS-based sequencing of DMD gene was done in 28 MLPA- negative cases (25 male probands with the DMD phenotype and 3 obligate carrier mothers of deceased affected male patients) and disease-causing variants were identified in 19 (67.9%) of these cases. Further molecular testing in four of the remaining nine cases revealed gene variants associated with limb girdle muscular dystrophies. Thus, NGS-based multigene panel testing for muscular dystrophy-associated genes or clinical exome sequencing rather than targeted DMD gene sequencing appears to be a more cost-effective testing modality with better diagnostic yield, for MLPA-negative patients with the DMD phenotype.

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Late-onset KMT2B-related dystonia in an Indian patient with normal cognition, dystonic opisthotonus and lack of oromandibular and laryngeal involvement

Parkinsonism Relat Disord, Vol. 74, Pages 33-35, 2020

PMID: 32305686

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Are shed hair genomes the most effective noninvasive resource for estimating relationships in the wild?

Ecol Evol, Vol. 10, Issue 11, Pages 4583-4594, 2020

PMID: 32551045

Knowledge of relationships in wild populations is critical for better understanding mating systems and inbreeding scenarios to inform conservation strategies for endangered species. To delineate pedigrees in wild populations, study genetic connectivity, study genotype-phenotype associations, trace individuals, or track wildlife trade, many identified individuals need to be genotyped at thousands of loci, mostly from noninvasive samples.

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Proteogenomics analysis unveils a TFG-RET gene fusion and druggable targets in papillary thyroid carcinomas

Nat Commun, Vol. 11, Issue 1, Pages 2056, 2020

PMID: 32345963

Papillary thyroid cancer (PTC) is the most common type of endocrine malignancy. By RNA-seq analysis, we identify a RET rearrangement in the tumour material of a patient who does not harbour any known RAS or BRAF mutations. This new gene fusion involves exons 1-4 from the 5' end of the Trk fused Gene (TFG) fused to the 3' end of RET tyrosine kinase leading to a TFG-RET fusion which transforms immortalized human thyroid cells in a kinase-dependent manner.

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Emerging biomarkers and clinical significance of HPV genotyping in prevention and management of cervical cancer

Microbial pathogenesis, Vol. 143, Pages 104131, 2020

PMID: 32169490

Cervical cancer is a growing and serious problem world-wide in women, but more acute in developing countries especially in Indian subcontinent. The main causative agent for the disease is Human Papilloma Virus (HPV). The history of the cervical cancer goes back to eighteenth century as the HPV infection is reported since 1800s.

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Whole genome enrichment approach for rapid detection of Mycobacterium tuberculosis and drug resistance-associated mutations from direct sputum sequencing

Tuberculosis (Edinb), Vol 121, Pages 101915, 2020

PMID: 32279871

Tuberculosis is the leading cause of death among infectious diseases worldwide. Detection of Mycobacterium tuberculosis (Mtb), using routine culture-based methods is time consuming resulting in delayed diagnosis and poor treatment outcomes. Currently available molecular tests provide faster diagnosis but are able to screen only limited hot-spot mutations. Whole genome sequencing from direct sputum offers a potential solution, however, due to the presence of other microbes and host DNA its use in diagnostic testing remains challenging.

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Factor XIII Deficiency with a Novel Nonsense Mutation

Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion, Vol. 36, Issue 3, Pages 588-589, 2020

PMID: 32647443

Factor XIII deficiency is a rare inherited autosomal recessive disorder and occurs at a frequency of approximately 1 in 1–5 million people [1]. During the last 4 decades, over 200 cases of congenital factor XIII (FXIII) deficiency have been reported in the literature [2, 3]. FXIII circulates as a tetramer of two FXIIIA and two FXIIIB subunits.

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Horizontal gaze palsy and progressive scoliosis-a tale of two siblings with ROBO3 mutation

Ophthalmic genetics, Vol. 41, Issue 1, Pages 99-100, 2020

PMID: 32077773

Horizontal gaze palsy with progressive scoliosis-1 (HGPPS1) is a rare autosomal recessive condition named after its clinical manifestations. HGPPS is due to ROBO3 mutation (OMIM number: 608630) and is characterized by brainstem maldevelopment which is responsible for its phenotypic presentation (1,2).

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Heterogeneity of Satellite Cells Implicates DELTA1/NOTCH2 Signaling in Self-Renewal

Cell reports, Vol. 30, Issue 5, Pages 1491-1503.e6. 2020

PMID: 32023464

How satellite cells and their progenitors balance differentiation and self-renewal to achieve sustainable tissue regeneration is not well understood. A major roadblock to understanding satellite cell fate decisions has been the difficulty of studying this process in vivo.

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Natural Killer cell transcriptome during primary EBV infection and EBV associated Hodgkin Lymphoma in children-A preliminary observation

Immunobiology, Vol. 225, Issue 3, Pages 151907, 2020

PMID: 32044149

Epstein Barr Viral infection is a common childhood infection in India and is also nearly 100 % etiologically associated with pediatric Hodgkin Lymphoma (HL). The main question in EBV immunobiology has been, why only a small subset of infected individuals develop EBV associated malignancies, while the vast majority carry this virus asymptomatically for life.

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Successful renal transplantation in a family with a novel mutation in COL4A3 gene and autosomal recessive Alport syndrome

Nephrology (Carlton, Vic.), Vol. 25, Issue 6, Pages 497-501, 2020

PMID: 31925849

Alport syndrome (AS) is an inherited disorder of basement membranes caused by mutations affecting specific proteins of the type IV collagen family, presenting with nephropathy and extrarenal manifestations such as sensorineural deafness and ocular anomalies.

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Erratum: Removal Notice to Slimming to the Death: Herbalife(R) Associated Fatal Acute Liver Failure – Heavy Metals, Toxic Compounds, Bacterial Contaminants and Psychotropic Agents in Products Sold in India, [J Clin Exp Hepatol 9 (2019) 268-272]

Journal of clinical and experimental hepatology, Vol. 10, Issue 1, Pages 100, 2020

PMID: 32025170

[This corrects the article DOI: 10.1016/j.jceh.2018.08.002.].

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A newly recognized multiple malformation syndrome with caudal regression associated with a biallelic c.402G>A variant in TBX4

European journal of human genetics : EJHG, Vol. 28, Issue 5, Pages 669-673, 2020

PMID: 31965066

The T-box4 (TBX4) gene (OMIM *601719) belongs to the T-box family of transcription regulators that share a conserved homology domain and are expressed at specific sites during various stages of embryonic development.

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Robinow Syndrome and Brachydactyly: An Interplay of High-Throughput Sequencing and Deep Phenotyping in a Kindred

Molecular syndromology, Vol. 11, Issue 1, Pages 43-49, 2020

PMID: 32256301

We report a family with a spectrum of short stature, craniofacial dysmorphism, and digital anomalies in a father and 2 daughters, with the youngest (proband) displaying a severe phenotype. Clinically, autosomal dominant Robinow syndrome (ADRS) was diagnosed. Whole-exome sequencing identified a heterozygous pathogenic BMP2 variant in the father and his daughters.

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Genetic analysis of familial hypercholesterolemia in Asian Indians: A single-center study

Journal of clinical lipidology, Vol. 14, Issue 1, Pages 35-45, 2020

PMID: 32044282

Familial hypercholesterolemia (FH), an autosomal codominant disorder characterized by very high low-density lipoprotein cholesterol, is strongly associated with premature coronary artery disease.

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The Indian cobra reference genome and transcriptome enables comprehensive identification of venom toxins

Nature genetics, Vol. 52, Issue 1, Pages 106-117, 2020

PMID: 31907489

Snakebite envenoming is a serious and neglected tropical disease that kills ~100,000 people annually. High-quality, genome-enabled comprehensive characterization of toxin genes will facilitate development of effective humanized recombinant antivenom. We report a de novo near- chromosomal genome assembly of Naja naja, the Indian cobra, a highly venomous, medically important snake.

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S100a4 upregulation in Pik3caH1047R;Trp53R270H;MMTV-Cre-driven mammary tumors promotes metastasis

Breast cancer research : BCR, Vol. 21, Issue 1, Pages 152, 2019

PMID: 31881983

PIK3CA mutations are frequent in human breast cancer. Pik3caH1047R mutant expression in mouse mammary gland promotes tumorigenesis. TP53 mutations co-occur with PIK3CA mutations in human breast cancers. We previously generated a conditionally activatable Pik3caH1047R;MMTV-Cre mouse model and found a few malignant sarcomatoid (spindle cell) carcinomas that had acquired spontaneous dominant-negative Trp53 mutations.

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Detection of clinically relevant epidermal growth factor receptor pathway mutations in circulating cell-free tumor DNA using next generation sequencing in squamous cell carcinoma lung

South Asian journal of cancer, Vol. 8, Issue 4, Pages 247-249, 2019

PMID: 31807490

Limited repertoires of targets are available in the management of squamous cell carcinoma lung. In this study, we analyzed epidermal growth factor receptor (EGFR), RAS, BRAF mutations in lung cancer patients of squamous cell histology using next-generation sequencing (NGS) on the circulating cell-free DNA (cf-DNA).

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MAP2K1 is a potential therapeutic target in erlotinib resistant head and neck squamous cell carcinoma

Nature Scientific reports, Vol. 9, Issue 1, Pages 18793, 2019

PMID: 31827134

Epidermal growth factor receptor (EGFR) targeted therapies have shown limited efficacy in head and neck squamous cell carcinoma (HNSCC) patients despite its overexpression. Identifying molecular mechanisms associated with acquired resistance to EGFR-TKIs such as erlotinib remains an unmet need and a therapeutic challenge.

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Prevalence of mutations in inherited retinal diseases: A comparison between the United States and India

Molecular genetics & genomic medicine, Vol. 8, Issue 2, Pages e1081, 2019

PMID: 31816670

Studies evaluating next-generation sequencing (NGS) for retinal disorders may not reflect clinical practice. We report results of retrospective analysis of patients referred for clinical testing at two institutions (US and India).

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Identification of African-Specific Admixture between Modern and Archaic Humans

American journal of human genetics, Vol. 105, Issue 6, Pages 1254-1261, 2019

PMID: 31809748

Recent work has demonstrated that two archaic human groups (Neanderthals and Denisovans) interbred with modern humans and contributed to the contemporary human gene pool. These findings relied on the availability of high-coverage genomes from both Neanderthals and Denisovans.

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The GenomeAsia 100K Project enables genetic discoveries across Asia

Nature, Vol. 576, Issue 7785, Pages 106-111, 2019

PMID: 31802016

The underrepresentation of non-Europeans in human genetic studies so far has limited the diversity of individuals in genomic datasets and led to reduced medical relevance for a large proportion of the world's population. Population-specific reference genome datasets as well as genome-wide association studies in diverse populations are needed to address this issue.

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Association of HLA-A, -B, DRB, and DQB Alleles with Persistent HPV-16 Infection in Women from Tamil Nadu, India

Viral immunology, Vol. 32, Issue 10, Pages 430-441, 2019

PMID: 31800372

Women with persistent human papillomavirus (HPV) infections have a high risk of developing cervical cancer (CaCx). HPV-16 alone accounts for more than 60% of CaCx worldwide. Most of the HPV infections are transient and only a subset of women develop persistent HPV-16 infection.

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More than the eye can see: Genomic insights into the drivers of genetic differentiation in Royal/Macaroni penguins across the Southern Ocean

Molecular Phylogenetics and Evolution, 2019

PMID: 31323335

In this study, we use genome-wide Single Nucleotide Polymorphisms to test genetic differentiation between these geographically isolated taxa and evaluate the main drivers of population structure among breeding colonies of macaroni/royal penguins. Genetic similarity observed between macaroni and royal penguins suggests they constitute a single evolutionary unit.

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Vitamin K1 prevents diabetic cataract by inhibiting lens aldose reductase 2 (ALR2) activity

Nature Scientific reports, Vol. 9, Issue 1, Pages 14684, 2019

PMID: 31604989

This study investigated the potential of vitamin K1 as a novel lens aldose reductase inhibitor in a streptozotocin-induced diabetic cataract model. A single, intraperitoneal injection of streptozotocin (STZ) (35 mg/kg) resulted in hyperglycemia, activation of lens aldose reductase 2 (ALR2) and accumulation of sorbitol in eye lens which could have contributed to diabetic cataract formation. However, when diabetic rats were treated with vitamin K1 (5 mg/kg, sc, twice a week) it resulted in lowering of blood glucose and inhibition of lens aldose reductase activity because of which there was a corresponding decrease in lens sorbitol accumulation.

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Irreversible Electroporation Combined with Checkpoint Blockade and TLR7 Stimulation Induces Antitumor Immunity in a Murine Pancreatic Cancer Model

Journal of Cancer Immunology Research, 7(10): 1714-1726, 2019

PMID: 31409607

Irreversible electroporation (IRE) is a nonthermal ablation technique that is used clinically in selected patients with locally advanced pancreatic cancer, but most patients develop recurrent distant metastatic disease. We hypothesize that IRE can induce an in situ vaccination effect by releasing tumor neoantigens in an inflammatory context. Using an immunocompetent mouse model, we demonstrated that IRE alone produced complete regression of subcutaneous tumors in approximately 20% to 30% of mice.

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Chronic Exposure to Chewing Tobacco Induces Metabolic Reprogramming and Cancer Stem Cell-Like Properties in Esophageal Epithelial Cells

Cells, Vol. 8, Issue 9, 2019

PMID: 31438645

Tobacco in its smoke and smokeless form are major risk factors for esophageal squamous cell carcinoma (ESCC). However, molecular alterations associated with smokeless tobacco exposure are poorly understood. In the Indian subcontinent, tobacco is predominantly consumed in chewing form.

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First report of THOC6 related intellectual disability (Beaulieu Boycott Innes syndrome) in two siblings from India

European journal of medical genetics, Vol. 63, Issue 3, Pages 103742, 2019

PMID: 31421288

THOC6 is a newly described causal gene for an autosomal recessive intellectual disability (ID) - Beaulieu Boycott Innes syndrome (BBIS) (OMIM # 613680). It is characterized by ID with dysmorphic facies, genitourinary, cardiac anomalies, and dentition problems. Here, we report the first two siblings of BBIS from the Indian subcontinent with previously unreported skeletal anomalies such as Sprengel shoulder, calcaneo valgus deformity, radioulnar dysostosis, and overlapping toes.

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Resequencing CYP2D6 gene in Indian population: CYP2D6*41 identified as the major reduced function allele

Pharmacogenomics, Vol. 20, Issue 10, Pages 719-729, 2019

PMID: 31368850

The CYP2D6 gene is highly polymorphic and harbors population specific alleles that define its predominant metabolizer phenotype. This study aimed to identify polymorphisms in Indian population owing to scarcity of CYP2D6 data in this population.

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Immunodeficiency, Motor Delay, and Hypouricemia Caused by a Novel Mutation of Purine Nucleoside Phosphorylase Gene in an Indian Infant

Annals of Indian Academy of Neurology, Vol. 22, Issue 2, Pages 231-233, 2019

PMID: 31007444

We describe an 11-month-old boy who presented with recurrent respiratory infections from 6 months of age. His elder sister died at 10 months with severe septicemia and meningitis. The boy had a mild motor delay. Investigations revealed T cell deficiency and very low serum uric acid suggestive of purine nucleoside phosphorylase (PNP) deficiency - a rare variant of severe combined immunodeficiency disease. A novel homozygous missense mutation of c.597C>G(p. S199R) of exon 5 on PNP gene confirmed the diagnosis. We suggest that uric acid should be a part of investigation profile for unidentified motor delay, as recurrent infections can be late presentation.

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Somatic Mutations Profile of a Young Patient With Metastatic Urothelial Carcinoma Reveals Mutations in Genes Involved in Ion Channels

Frontiers in oncology, Vol. 9, Pages 435, 2019

PMID: 31192134

Urothelial carcinoma is the most common malignancy of the bladder and is primarily considered as a disease of the elderly. Studies that address bladder tumor occurrence in young age groups are rare.

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Whole Genome Sequencing and Comparative Genomic Analysis Reveal Allelic Variations Unique to a Purple Colored Rice Landrace (Oryza sativa ssp. indica cv. Purpleputtu)

Frontiers in plant science, Vol. 10, Pages 513, 2019

PMID: 31134103

Purpleputtu (Oryza sativa ssp. indica cv. Purpleputtu) is a unique rice landrace from southern India that exhibits predominantly purple color. This study reports the underlying genetic complexity of the trait, associated domestication and de-domestication processes during its coevolution with present day cultivars.

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Methylglyoxal – An emerging biomarker for diabetes mellitus diagnosis and its detection methods

Biosensors & bioelectronics, Vol. 133, Pages 107-124, 2019

PMID: 30921627

Diabetes Mellitus (DM) is one among the supreme metabolic issues observed in history since 3000 BCE and has gained much interest recently due to the increasing number of diabetic cases every year. Glucose is considered as the most iconic biomarker for diabetes detection, and fluctuations in its levels are related to different stages of DM.

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Non-coding and Coding Transcriptional Profiles Are Significantly Altered in Pediatric Retinoblastoma Tumors

Frontiers in oncology, Vol. 9, Pages 221, 2019

PMID: 31058073

Retinoblastoma is a rare pediatric tumor of the retina, caused by the homozygous loss of the Retinoblastoma 1 (RB1) tumor suppressor gene. Previous microarray studies have identified changes in the expression profiles of coding genes; however, our understanding of how non-coding genes change in this tumor is absent.

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Role of VEGF165b/VEGFTOTAL ratio in gestational diabetes mellitus

Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, Vol. 35, Issue 9, Pages 811-814, 2019

PMID: 30964350

Proper vascular function is important for well-being of mother and growing fetus. VEGFTOTAL, and VEGF165b levels and its vascular endothelial complications in gestational diabetes mellitus (GDM) together with the association of inflammation and advanced glycation end products (AGEs) are less studied. VEGF165b/VEGFTOTAL (VEGF RATIO) in GDM pregnant women was investigated in this study.

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Simultaneous diagnosis of unilateral retinoblastoma and contralateral optic pathway glioma in a child with neurofibromatosis type 1

Pediatric hematology and oncology, Vol. 36, Issue 2, Pages 82-85, 2019

PMID: 30963792

A 2.5-year-old girl presented with redness and swelling of the right-eye for 7-days (Figure 1A). Examination revealed an intraocular mass with anterior segment seeding. The other eye was normal. A diagnosis of unilateral retinoblastoma (RB) manifesting as orbital cellulitis was considered

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First International Conference on RASopathies and Neurofibromatoses in Asia: Identification and advances of new therapeutics

American journal of medical genetics. Part A, Vol. 179, Issue 6, Pages 1091-1097, 2019

PMID: 30908877

The neurofibromatoses, which include neurofibromatosis type I (NF1), neurofibromatosis type II (NF2), and schwannomatosis, are a group of syndromes characterized by tumor growth in the nervous system. The RASopathies are a group of syndromes caused by germline mutations in genes that encode components of the RAS/mitogen-activated protein kinase (MAPK) pathway.

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Adult-Onset Myoclonus-Dystonia Syndrome Preceding Characteristic Facial Myoclonus in Indian ADCY5-related Dyskinesia

Movement disorders clinical practice, Vol. 6, Issue 3, Pages 267-268, 2019

PMID: 33999972

A 21‐year‐old man presented to us with involuntary jerking movements of his hands and head that started at the age of 13. In the early years, the movements would come in intermittent spells, and sometimes his whole body would tremble when anxious, concentrating on an activity, or riding his scooter.

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A Synthetic DNA, Multi-Neoantigen Vaccine Drives Predominately MHC Class I CD8(+) T-cell Responses, Impacting Tumor Challenge

Cancer immunology research, Vol. 7, Issue 2, Pages 174-182, 2019

PMID: 30679156

T-cell recognition of cancer neoantigens is important for effective immune-checkpoint blockade therapy, and an increasing interest exists in developing personalized tumor neoantigen vaccines. Previous studies utilizing RNA and long-peptide neoantigen vaccines in preclinical and early-phase clinical studies have shown immune responses predominantly driven by MHC class II CD4(+) T cells.

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Novel GNAL mutation in an Indian patient with generalized dystonia and response to deep brain stimulation

Parkinsonism & related disorders, Vol. 62, Pages 246-247, 2019

PMID: 30660597

Mutations in GNAL have been associated with cranio-cervical dystonia (DYT-GNAL) [ [1] ]. The dystonia most often progresses to involve other regions, particularly the face and laryngeal muscles and less commonly the trunk, arm and lower limbs. The clinical phenotype in GNAL-related dystonia appears to be similar to that caused by mutations in THAP1 [ [2] ]

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Differential methylation of the type 2 diabetes susceptibility locus KCNQ1 is associated with insulin sensitivity and is predicted by CpG site specific genetic variation

Diabetes research and clinical practice, Vol. 148, Pages 189-199, 2019

PMID: 30641161

Epigenetic mechanisms regulate gene expression and may influence the pathogenesis of type 2 diabetes through the loss of insulin sensitivity. The aims of this study were to measure variation in DNA methylation at the type 2 diabetes locus KCNQ1 and assess its relationship with metabolic measures and with genotype.

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A Computational Approach Identifies Immunogenic Features of Prognosis in Human Cancers

Frontiers in immunology, Vol. 9, Pages 3017, 2018

PMID: 30622534

A large number of tumor intrinsic and extrinsic factors determine long- term survival in human cancers. In this study, we stratified 9120 tumors from 33 cancers with respect to their immune cell content and identified immunogenomic features associated with long-term survival.

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Metabolite systems profiling identifies exploitable weaknesses in retinoblastoma

FEBS letters, Vol. 593, Issue 1, Pages 23-41, 2018

PMID: 30417337

Retinoblastoma (RB) is a childhood eye cancer. Currently, chemotherapy, local therapy, and enucleation are the main ways in which these tumors are managed. The present work is the first study that uses constraint- based reconstruction and analysis approaches to identify and explain RB- specific survival strategies, which are RB tumor specific. Importantly, our model-specific secretion profile is also found in RB1-depleted human retinal cells in vitro and suggests that novel biomarkers involved in lipid metabolism may be important. Finally, RB-specific synthetic lethals have been predicted as lipid and nucleoside transport proteins that can aid in novel drug target development.

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Actionable Activating Oncogenic ERBB2/HER2 Transmembrane and Juxtamembrane Domain Mutations

Cancer cell, Vol. 34, Issue 5, Pages 792-806.e5, 2018

PMID: 30449325

Deregulated HER2 is a target of many approved cancer drugs. We analyzed 111,176 patient tumors and identified recurrent mutations in HER2 transmembrane domain (TMD) and juxtamembrane domain (JMD) that include G660D, R678Q, E693K, and Q709L.

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Is there a Chance to Promote Arteriogenesis by DPP4 Inhibitors Even in Type 2 Diabetes? A Critical Review

Cells, Vol. 7, Issue 10, 2018

PMID: 30360455

Cardiovascular diseases (CVD) are still the prevailing cause of death not only in industrialized countries, but even worldwide. Type 2 diabetes mellitus (type 2 DM) and hyperlipidemia, a metabolic disorder that is often associated with diabetes, are major risk factors for developing CVD. Recently, clinical trials proved the safety of gliptins in treating patients with type 2 DM.

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A neoepitope derived from a novel human germline APC gene mutation in familial adenomatous polyposis shows selective immunogenicity

PloS one, Vol. 13, Issue 9, Pages e0203845, 2018

PMID: 30256815

Familial adenomatous polyposis (FAP) is an inherited condition arising from genetic defects in the Adenomatous polyposis coli (APC) gene. Carriers with mutations in the APC gene develop polyps in the colon and rectum which if not managed, transition into colon cancer. In this study, we identified a novel germline mutation in the APC gene in members of an FAP-affected (Familial adenomatous polyposis) family.

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Progressive nonparoxysmal chorea and dystonia due to myofibrillogenesis regulator-1 gene mutation

Parkinsonism & related disorders, Vol. 60, Pages 186-187, 2018

PMID: 30174277

Mutations in the myofibrillogenesis regulator gene (MR-1) causes paroxysmal non -kinesigenic dyskinesia (PNKD) characterized by episodic (paroxysmal) attacks of any combination of chorea, dystonia and athetosis (MR-1/PNKD) [1]. This gene is transcribed into three alternatively spliced isoforms: long (MR-1L), medium (MR-1M) and small (MR-1S) [2,3].

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A cancer vaccine approach for personalized treatment of Lynch Syndrome

Nature Scientific reports, Vol. 8, Issue 1, Pages 12122, 2018

PMID: 30108227

Lynch syndrome (LS) is a cancer predisposition disorder wherein patients have a 70-80% lifetime risk of developing colorectal cancers (CRC). Finding germline mutations in predisposing genes allows for risk assessment of CRC development. Here we report a germline heterozygous frame-shift mutation in the mismatch repair MLH1 gene which was identified in members of two unrelated LS families.

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Next generation sequencing identifies novel disease-associated BEST1 mutations in Bestrophinopathy patients

Nature Scientific reports, Vol. 8, Issue 1, Pages 10176, 2018

PMID: 29976937

Bestinopathies are a spectrum of retinal disorders associated with mutations in BEST1 including autosomal recessive bestrophinopathy (ARB) and autosomal dominant Best vitelliform macular dystrophy (BVMD). We applied whole-exome sequencing on four unrelated Indian families comprising eight affected and twelve unaffected individuals.

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Identification of deletion-duplication in HEXA gene in five children with Tay-Sachs disease from India

BMC medical genetics, Vol. 19, Issue 1, Pages 109, 2018

PMID: 29973161

Tay-Sachs disease (TSD) is a sphingolipid storage disorder caused by mutations in the HEXA gene. To date, nearly 170 mutations of HEXA have been described, including only one 7.6 kb large deletion.

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Complete mitogenome reveals genetic divergence and phylogenetic relationships among Indian cattle (Bos indicus) breeds

Animal biotechnology, Vol. 30, Issue 3, Pages 219-232, 2018

PMID: 29938580

Indigenous cattle of India belong to the species, Bos indicus and they possess various adaptability and production traits. However, little is known about the genetic diversity and origin of these breeds. To investigate the status, we sequenced and analyzed the whole mitochondrial DNA (mtDNA) of seven Indian cattle breeds.

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Noninvasive prenatal testing (NIPT) detects variant of Turner syndrome not detectable by fluorescent in situ hybridization

The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians, Vol. 32, Issue 24, Pages 4177-4180, 2018

PMID: 29793366

Noninvasive prenatal testing (NIPT) is a reliable screening method for fetal aneuploidy detection of trisomy 18, 13, 21 along with few sex chromosome abnormalities monosomy X, XXX, XXY (Klinefelter), XYY (Jacob) syndromes and certain microdeletions which include cri-du-chat, DiGeorge, 1p36, Angelman, and Prader-Willi syndromes in comparison to the available screening methods.

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Molecular alterations associated with chronic exposure to cigarette smoke and chewing tobacco in normal oral keratinocytes

Cancer biology & therapy, Vol. 19, Issue 9, Pages 773-785, 2018

PMID: 29723088

Tobacco usage is a known risk factor associated with development of oral cancer. It is mainly consumed in two different forms (smoking and chewing) that vary in their composition and methods of intake. Despite being the leading cause of oral cancer, molecular alterations induced by tobacco are poorly understood.

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Becker’s Hospital Review: Tumor microenvironment is a powerful companion diagnostic for cancer immunotherapy applications

Becker's Hospital Review, 2018

Currently approved checkpoint inhibitors are antibodies that block the function of three key proteins expressed on the surface of T cells: CTLA-4, PD-1 and PD-L1. Under normal conditions, these proteins function as brakes to prevent immune-related toxicity from arising because of persistent T cell activity. Cancer hijacks this essential function   of immune homeostasis to protect itself from immune- mediated elimination [1, 2]. By expressing high levels of PD- L1, tumor cells engage PD-1 receptors on T cells, suppressing  their anti-tumor activity and escaping T cell-mediated killing. By blocking PD-1 and PD-L1 signaling, the checkpoint inhibitors remove the brakes on T cells imposed by the tumor and enhance their anti-tumor activity

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Clinical, Immunological, and Molecular Findings in Five Patients with Major Histocompatibility Complex Class II Deficiency from India

Front Immunol, 16:9:188, 2018

PMID: 29527204

Major histocompatibility complex (MHC) class II deficiency is a rare autosomal recessive form of primary immunodeficiency disorder (PID) characterized by the deficiency of MHC class II molecules. This deficiency affects the cellular and humoral immune response by impairing the development of CD4+ T helper (Th) cells and Th cell-dependent antibody production by B cells.

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Comprehensive genomic analysis identifies pathogenic variants in maturity-onset diabetes of the young (MODY) patients in South India

BMC medical genetics, Vol. 19, Issue 1, Pages 22, 2018

PMID: 29439679

Maturity-onset diabetes of the young (MODY) is an early- onset, autosomal dominant form of non-insulin dependent diabetes. Genetic diagnosis of MODY can transform patient management. Earlier data on the genetic predisposition to MODY have come primarily from familial studies in populations of European origin.

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The complete mitochondrial genome of Indian cattle (Bos indicus)

Mitochondrial DNA. Part B, Resources, Vol. 3, Issue 1, Pages 207-208, 2018

PMID: 33490497

India has 40 distinct zebuine cattle breeds with different adaptability and production traits. In the present study, we report the complete mitochondrial genome sequence of Indian cattle for the first time. The mitogenome contains 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes and a control region (D-loop region).

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Single Nucleotide Polymorphism-Based Noninvasive Prenatal Testing: Experience in India

Journal of obstetrics and gynaecology of India, Vol. 68, Issue 6, Pages 462-470, 2018

PMID: 30416273

Noninvasive prenatal testing (NIPT) has revolutionized prenatal screening for chromosomal aneuploidies in some countries. Its implementation has been sporadic in developing countries. Given the genetic variation of the people in different countries, we evaluated the performance of the SNP-based NIPT in India.

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Ancient Human Migrations to and through Jammu Kashmir- India were not of Males Exclusively

Nature Scientific Reports, Vol. 8, No. 851, 2018

PMID: 29339819

Jammu and Kashmir (J&K), the Northern most State of India, has been under-represented or altogether absent in most of the phylogenetic studies carried out in literature, despite its strategic location in the Himalayan region. Nonetheless, this region may have acted as a corridor to various migrations to and from mainland India, Eurasia or northeast Asia.

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Validation of liquid biopsy: plasma cell-free DNA testing in clinical management of advanced non-small cell lung cancer

Lung Cancer (Auckland, N.Z.), Vol. 9, Pages 1-11, 2018

PMID: 29379323

Plasma cell-free tumor DNA, or circulating tumor DNA (ctDNA), from liquid biopsy is a potential source of tumor genetic material, in the absence of tissue biopsy, for EGFR testing. Our validation study reiterates the clinical utility of ctDNA next generation sequencing (NGS) for EGFR mutation testing in non-small cell lung cancer (NSCLC).

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A novel splice variant in EMC1 is associated with cerebellar atrophy, visual impairment, psychomotor retardation with epilepsy

Molecular genetics & genomic medicine, Vol. 6, Issue 2, Pages 282-287, 2017

PMID: 29271071

Several genes have been implicated in a highly variable presentation of developmental delay with psychomotor retardation. Mutations in EMC1 gene have recently been reported. Herein, we describe a proband born of a consanguineous marriage, who presented with early infantile onset epilepsy, scaphocephaly, developmental delay, central hypotonia, muscle wasting, and severe cerebellar and brainstem atrophy.

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A non-enzymatic two step catalytic reduction of methylglyoxal by nanostructured V2O5 modified electrode

Biosensors & bioelectronics, Vol. 103, Pages 143-150, 2017

PMID: 29291594

Methylglyoxal (MG) is a predominant precursor for advanced glycation end products (AGEs) due to its protein glycation reactions, which are the major causes of diabetic complications. MG is explored as a significant biomarker towards the prediction of diabetic complications.

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Erratum to: Asparagine synthetase deficiency-report of a novel mutation and review of literature

Metabolic brain disease, Vol. 32, Issue 6, Pages 1901, 2017

PMID: 28875262

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Serum starvation of ARPE-19 changes the cellular distribution of cholesterol and Fibulin3 in patterns reminiscent of age-related macular degeneration

Experimental cell research, Vol. 361, Issue 2, Pages 333-341, 2017

PMID: 29097185

Retinal pigment epithelium (RPE) has been implicated as key source of cholesterol-rich deposits at Bruch's membrane (BrM) and in drusen in aging human eye. We have shown that serum-deprivation of confluent RPE cells is associated with upregulation of cholesterol synthesis and accumulation of unesterified cholesterol (UC).

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Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS)-First Report of Clinical and Imaging Features from India, and a Novel SACS Gene Duplication

Movement disorders clinical practice, Vol. 4, Issue 5, Pages 775-777, 2017

PMID: 30838287

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The utility and futility of targeted next generation sequencing for carrier detection in “At Risk” couples

Genetic Clinics 2017, Vol 10, Issue 1, 2017

Next generation sequencing has changed the approach to genetic diagnosis and testing in recent times. The days have arrived when a molecular genetic diagnosis can be attempted even without the availability of the proband or affected person. However this requires additional strong evidence of diagnosis in the proband, such as biochemical or radiological hallmarks. Needless to say, this attempt should always be made during counseling to make the family aware of the fallacies and limitation involved due to non-availability of the sample of the proband.

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Next-Generation Sequencing Reveals Novel Mutations in X-linked Intellectual Disability

Omics : a journal of integrative biology, Vol. 21, Issue 5, Pages 295-303, 2017

PMID: 28481730

Robust diagnostics for many human genetic disorders are much needed in the pursuit of global personalized medicine. Next-generation sequencing now offers new promise for biomarker and diagnostic discovery, in developed as well as resource-limited countries.

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A splice site mutation in HERC1 leads to syndromic intellectual disability with macrocephaly and facial dysmorphism: Further delineation of the phenotypic spectrum

American journal of medical genetics. Part A, Vol. 170, Issue 7, Pages 1868-1873, 2016

PMID: 27108999

We report on a sib pair of Indian origin presenting with intellectual disability, dysmorphism, and macrocephaly. Exome sequencing revealed a homozygous splice site HERC1 mutation in both probands. Functional analysis revealed use of an alternate splice site resulting in formation of a downstream stop codon and nonsense mediated decay. In the light of recent reports of HERC1 mutations in two families with a similar phenotypic presentation, this report reiterates the pathogenic nature and clinical consequences of HERC1 disruption. (c) 2016 Wiley Periodicals, Inc.

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Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations

Nature genetics, Vol. 48, Issue 4, Pages 407-416, 2016

PMID: 26928227

We analyzed transcriptomes (n = 211), whole exomes (n = 99) and targeted exomes (n = 103) from 216 malignant pleural mesothelioma (MPM) tumors. Using RNA-seq data, we identified four distinct molecular subtypes: sarcomatoid, epithelioid, biphasic-epithelioid (biphasic-E) and biphasic- sarcomatoid (biphasic-S).

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The expression dynamics of mechanosensitive genes in extra-embryonic vasculature after heart starts to beat in chick embryo

Biorheology, Vol. 53, Issue 1, Pages 33-47, 2016

PMID: 26889656

Fluid flow plays an important role in vascular development. However, the detailed mechanisms, particularly the link between flow and modulation of gene expression during vascular development, remain unexplored. In chick embryo, the key events of vascular development from initiation of heart beat to establishment of effective blood flow occur between the stages HH10 and HH13.

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A novel H395R mutation in MKKS/BBS6 causes retinitis pigmentosa and polydactyly without other findings of Bardet-Biedl or McKusick-Kaufman syndrome

Molecular vision, Vol. 22, Pages 73-81, 2016

PMID: 26900326

To identify the causative mutation in two siblings from a consanguineous family in India with retinitis pigmentosa (RP) and polydactyly without other findings of Bardet-Biedl syndrome (BBS). We also performed functional characterization of the mutant protein to explore its role in this limited form of BBS.

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First Report of Kufor-Rakeb Syndrome (PARK 9) from India, and a Novel Nonsense Mutation in ATP13A2 Gene

Movement disorders clinical practice, Vol. 2, Issue 3, Pages 326-327, 2015

PMID: 30838237

Kufor-Rakeb syndrome (KRS; PARK 9) is a rare autosomal-recessive form of juvenile-onset Parkinson's disease (PD) caused by ATP13A2 gene mutations. The classical description of KRS is that of rapidly progressive symptoms in the form of parkinsonism, spasticity, supranuclear upgaze paresis, facial-faucial-finger minimyoclonus, visual hallucinations, oculogyric dystonic spasms, and dementia, usually noted between 12 and 16 years of age, resulting in early severe motor handicap.[1]

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Identification of Novel Mutations in ABCA4 Gene: Clinical and Genetic Analysis of Indian Patients with Stargardt Disease

BioMed research international, Vol. 2015, Pages 940864, 2015

PMID: 25922843

Stargardt disease (STGD) is the leading cause of juvenile macular degeneration associated with progressive central vision loss, photophobia, and colour vision abnormalities. In this study, we have described the clinical and genetic features of Stargardt patients from an Indian cohort. The next generation sequencing was carried out in five clinically confirmed unrelated patients and their family members using a gene panel comprising 184 retinal specific genes.

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Evolution of targeted therapies in cancer: opportunities and challenges in the clinic

Future oncology (London, England), Vol. 11, Issue 2, Pages 279-293, 2015

PMID: 25591839

Targeted therapies have changed the course of cancer treatment in recent years. By reducing toxicity and improving outcome, these new generations of precision medicines have extended patient lives beyond what could be achieved by the use of nontargeted therapies. In the last 2 years, several new molecular entities targeting signaling proteins and immune pathways have gone through successful clinical development resulting in their approval. These new targeted therapies require patient selection and the discovery of biomarkers of response. This review discusses the evolution of targeted therapies in cancer and challenges in translating the concepts into clinical practice.

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Regulation of Macrophage Polarization by RON Receptor Tyrosine Kinase Signaling

Frontiers in immunology, Vol. 5, Pages 546, 2014

PMID: 25400637

The M1 and M2 states of macrophage polarization are the two extremes of a physiologic/phenotypic continuum that is dynamically influenced by environmental signals. The M1/M2 paradigm is an excellent framework to understand and appreciate some of the diverse functions that macrophages perform. Molecular analysis of mouse and human macrophages indicated that they gain M1 and M2-related functions after encountering specific ligands in the tissue environment. In this perspective, I discuss the function of recepteur d'origine nantais (RON) receptor tyrosine kinase in regulating the M2-like state of macrophage activation Besides decreasing pro- inflammatory cytokine production in response to toll-like receptor-4 activation, macrophage-stimulating protein strongly suppresses nitric oxide synthase and at the same time upregulates arginase, which is the rate limiting enzyme in the ornithine biosynthesis pathway. Interestingly, RON signaling preserved some of the characteristics of the M1 state, while still promoting the hallmarks of M2 polarization. Therefore, therapeutic modulation of RON activity can shift the activation state of macrophages between acute and chronic inflammatory states.

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Cost-efficient HIV-1 drug resistance surveillance using multiplexed high-throughput amplicon sequencing: implications for use in low- and middle-income countries

Journal of Antimicrobial Chemotherapy, Volume 69, Issue 12, Pages 3349–3355, 2014

PMID: 25085657

Increased trends of primary drug resistance mutations (DRMs) among treatment-naive HIV-1-infected patients in low- and middle-income countries (LMICs) and the non-availability of pre-antiretroviral therapy (ART) genotypic resistance testing (GRT) may severely affect future therapeutic outcomes. The main objective of this study was therefore to develop a simplified, cost- and labor-efficient but high-throughput GRT protocol to be applied in the large-scale surveillance of DRMs in LMICs.

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Prevalence of genetic variants associated with cardiovascular disease risk and drug response in the Southern Indian population of Kerala

Indian journal of human genetics, Vol. 20, Issue 2, Pages 175-184, 2014

PMID: 25400347

This study reports the prevalence of five clinically significant variants associated with increased risk of cardiovascular disorders, and variable responses of individuals to commonly prescribed cardiovascular drugs in a South Indian population from the state of Kerala.

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