Publications

Familial Cancer 24, 13 (2025), Dec 19, 2024

PMID: 39702679

Lynch syndrome (LS) is an autosomal dominant hereditary cancer predisposition syndrome whereby the lifetime risk of developing gastrointestinal and genitourinary cancers rises by to over 50%. It is caused by heterozygous variants in the DNA mismatch repair genes- MLH1, MSH2, MSH6 and PMS2, with the majority detected in MLH1 and MSH2. Recurrently observed LS-associated variants in apparently unrelated individuals have either arisen de novo in different families due to mutation hotspots or are inherited from a common ancestor (founder) that lived several generations back. Testing for founder variants can facilitate molecular diagnosis of LS more efficiently and cost effectively than screening for all possible variants in the MMR genes.

Am J Med Genet A. 2024, Dec 10, 2024

PMID: 39655693

BMJ Case Reports CP 2024;17:e260238

PMID: 39631901

We report a male child with developmental delay, microcephaly and facial dysmorphism in the form of a turri-brachycephaly-shaped skull, triangular face, posteriorly rotated lop ears, thick bushy eyebrows, synophrys, long deep philtrum and prominent incisors. The mobile application Face2Gene was used to screen the patient's facial photographs for known syndromes. The application suggested a high likelihood of KBG syndrome.

Ann Indian Acad Neurol. Dec 2, 2024

PMID: 39620998

Progressive supranuclear palsy (PSP) has emerged as a key area of interest among researchers worldwide, including those in India, who have actively studied the disorder over the past several decades. This review meticulously explores the extensive range of Indian research on PSP up to the present and offers insights into both current initiatives and potential future directions for managing PSP within the region.

Indian J Endocr Metab 2024;28:4807, Nov 8, 2024

PMID: 39676784

Maturity-onset diabetes of the young (MODY) is a rare group of disorders characterised by impaired functions or development of pancreatic islets and monogenic diabetes at a young age. Diagnosing MODY can be rewarding for both clinicians and patients as it can change the management from generic to targeted therapy.

Front Immunol, Vol.15, Article Number: 1466276, 2024

PMID: 39497832

Large granular lymphocyte (LGL) leukemia is a rare hematologic malignancy characterized by clonal expansion of cytotoxic T-cells frequent somatic activating STAT3 mutations. Based on the disease overlap between LGL leukemia rheumatoid arthritis (RA)a putative role for CD8+ T-cells in RA we hypothesized that STAT3 mutations may be detected in RA patient CD8+ T-cells correlate with clinical characteristics. Blood samples, clinical parameters, and demographics were collected from 98 RA patients and 9 healthy controls (HCs). CD8+ cell DNA was isolated and analyzed via droplet digital (dd)PCR to detect STAT3 mutations common in LGL leukemia: Y640F, D661Y, and the S614 to G618 region. STAT3 data from 99 HCs from a public dataset supplemented our 9 HCs.

Indian J Pediatr, 2024

PMID: 39425824

To evaluate the molecular aberrations at 11p15.5 locus in thirty-two patients with isolated lateralized overgrowth (ILO). Among selected 32 cases of ILO, methylation-sensitive multiplex ligation-dependent probe amplification (MS-MLPA) was performed initially followed by short tandem repeats (STR) marker analysis to confirm uniparental disomy (UPD). In those patients with normal MLPA reports, cyclin dependent kinase inhibitor 1C (CDKN1C) gene and whole exome sequencing was performed.

Hum Reprod Open, Vol. 2024, Issue 4, Article Number: hoae057, 2024

PMID: 39411542

What is the frequency of PLCZ1, ACTL7A, and ACTL9 variants in male patients showing fertilization failure after ICSI, and how effective is assisted oocyte activation (AOA) for them?. Male patients with fertilization failure after ICSI manifest variants in PLCZ1 (29.09%), ACTL7A (14.81%), and ACTL9 (3.70%), which can be efficiently overcome by AOA treatment with ionomycin.

Am J Med Genet A, Article Number: e63907, 2024

PMID: 39404460

We aimed to describe the clinical and genetic characteristics of 16 individuals with KBG syndrome (KBGS) from 13 Indian families. We retrospectively analyzed the clinical details of individuals with KBGS harboring a likely pathogenic/pathogenic variant in ANKRD11. We also analyzed their facial gestalt using Face2Gene and recorded the top three differential disorders suggested by the application.

Parkinsonism Relat Disord, Vol. 128, Article Number: 107152, 2024

PMID: 39326284

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) has been described in the literature mostly as early-onset leukodystrophy with cerebellar ataxia being the main clinical phenotype. However, other associated movement disorders have also been reported discretely. Here, we present seven cases of MLC.

Pediatr Nephrol, 2024

PMID: 39278986

Next-generation sequencing has enabled non-invasive diagnosis of type IV collagen disease in clinical settings other than the typical presentation of Alport syndrome (AS). We reviewed the clinical and histological records of children diagnosed with Alport syndrome based on next-generation sequencing. Variants on clinical exome sequencing were categorized using ACMG 2015 criteria.

Mol Biol Rep, Vol. 51, Issue 1, Article Number: 972, 2024

PMID: 39249557

Multiple myeloma, a complex hematologic malignancy, has devastating consequences for patients, including dramatic bone loss, severe bone pain, and pathological fractures that markedly decrease the quality of life and impact the survival of affected patients. This necessitates a refined understanding of biomarkers for accurate diagnosis and prognosis of such severe malignancy. Therefore, this article comprehensively covers current research, elucidating the diverse spectrum of biomarkers employed in clinical settings.

HLA, Vol. 104, Issue 3, Article Number: e15676, 2024

PMID: 39234804

Nine novel HLA alleles were identified when HLA typing individuals from the Indian population.

J Neuromuscul Dis, 2024

PMID: 39213088

GNE myopathy is a rare slowly progressive adult-onset distal myopathy with autosomal recessive inheritance. It has distinctive features of quadriceps sparing with preferential anterior tibial involvement. Most patients eventually become wheelchair bound by 10-20 years after onset. This study analyzes the phenotype-genotype characteristics and disease progression in a large cohort of GNEM patients from India.

HLA, Vol. 104, Issue 2, Article Number: e15656, 2024

PMID: 39189248

Extended sequences for 13 HLA alleles were found which had limited coverage previously.

J Parasit Dis, Vol 48, Issue 3, Pages 493-500, 2024

PMID: 39145370

Cases of imported malaria are reported each year in several malaria non-endemic countries, including Kuwait. PCR testing is the ideal method for identification of the infecting Plasmodium spp. The present study documented the epidemiologic characteristics of molecularly confirmed cases of imported malaria in Kuwait during the first year of COVID-19 pandemic. Malaria diagnosis was made by microscopy of blood-stained smears and confirmed by a multiplex real-time PCR assay. Samples with discordant species identification results were sequenced. A total of 27 cases (27%) [P. falciparum, 14; P. vivax, 11; P. ovale, 1; mixed P. falciparum and P. malariae, 1] were detected, of whom 12 came to Kuwait for the first time and 15 were returning after visiting their home countries. Most of the returning travelers (12 out of 15 cases, 80%) had not received malaria chemoprophylaxis. Most cases of falciparum malaria (13/15) were Africans while most of the vivax cases (9/11) were Asians. Malaria was more common among subjects entering Kuwait for the first time (OR = 4.025, CI 1.07,15.1) and illiterates (OR = 13.8, CI 1.8,101.4). In conclusion, imported malaria caused mainly by P. falciparum and P. vivax was an ongoing problem during the COVID-19 pandemic. Travel history and education level were significant predictors of malaria among suspected cases.

Indian Heart J, 2024

PMID: 39009076

This study aims to analyze the results of comprehensive genetic testing in patients presenting to a dedicated multidisciplinary inherited heart disease clinic in India.

Antib Ther, Vol. 7, Issue 3, Pages 256-265, 2024

PMID: 39262441

Recombinant antibodies (rAbs) have emerged as a promising solution to tackle antigen specificity, enhancement of immunogenic potential and versatile functionalization to treat human diseases. The development of single chain variable fragments has helped accelerate treatment in cancers and viral infections, due to their favorable pharmacokinetics and human compatibility.

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.

J Neuromuscul Dis, Pages 1-23, 2024

PMID: 38968056

Congenital myopathies (CMs) are a diverse group of inherited muscle disorders with broad genotypic and phenotypic heterogeneity. While the literature on CM is available from European countries, comprehensive data from the Indian subcontinent is lacking. This study aims to describe the clinical and histopathological characteristics of a cohort of genetically confirmed CMs from India and attempts to do phenotype-genotype correlation.

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

PMID: 38880420

Catalogues of pathogenic genetic mutations in hypertrophic cardiomyopathy (HCM) are disproportionately small when compared to that of the size of the population with South Asian ancestry and their collective increased risk of heart disease. We conducted clinical exome sequencing of 200 HCM patients to identified cardiomyopathy-associated genetic mutations.

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

PMID: 38903861

Cancer, a collection of more than two hundred different diseases, remains a leading cause of morbidity and mortality worldwide. Usually detected at the advanced stages of disease, metastatic cancer accounts for 90% of cancer-associated deaths. Therefore, the early detection of cancer, combined with current therapies, would have a significant impact on survival and treatment of various cancer types. Epigenetic changes such as DNA methylation are some of the early events underlying carcinogenesis. Here, we report on an interpretable machine learning model that can classify 13 cancer types as well as non-cancer tissue samples using only DNA methylome data, with 98.2% accuracy.

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).

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).

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.

Blood Cancer Discov, 2023

PMID: 38150184

Myeloid neoplasms arise from preexisting clonal hematopoiesis (CH); however, the role of CH in the pathogenesis of acute lymphoblastic leukemia (ALL) is unknown. We found that 18% of adult ALL cases harbored TP53, and 16% had myeloid CH-associated gene mutations. ALL with myeloid mutations (MyM) had distinct genetic and clinical characteristics, associated with inferior 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.

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.

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

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.

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.

Clinical and Experimental Dermatology, llad364, 2023

PMID: 37878805

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.

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.

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.

Nature, Vol. 618, Issue 7963, Pages 110-117, 2023

PMID: 37198475

A central question in evolutionary biology is whether sponges or ctenophores (comb jellies) are the sister group to all other animals. These alternative phylogenetic hypotheses imply different scenarios for the evolution of complex neural systems and other animal-specific traits. Conventional phylogenetic approaches based on morphological characters and increasingly extensive gene sequence collections have not been able to definitively answer this question. Here we develop chromosome-scale gene linkage, also known as synteny, as a phylogenetic character for resolving this question.

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.

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.

Human Mutation, Vol. 2023, Article Number: 362273, 2023

The sarcoglycanopathies are autosomal recessive limb-girdle muscular dystrophies (LGMDs) caused by the mutations in genes encoding the α, β, γ, and δ proteins which stabilizes the sarcolemma of muscle cells. The clinical phenotype is characterized by progressive proximal muscle weakness with childhood onset. Muscle biopsy findings are diagnostic in confirming dystrophic changes and deficiency of one or more sarcoglycan proteins. In this study, we summarized 1,046 LGMD patients for which a precise diagnosis was identified using targeted sequencing.

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.

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].

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.

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.

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.

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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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}

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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).

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.

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.

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.

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.

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]

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.

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.

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.

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).

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.

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.

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

PMID: 29527204

Hemophagocytic lymphohistiocytosis (HLH) is an immune dysregulation syndrome marked by immune hyperactivation, excessive cytokine release, and systemic inflammation. Familial HLH (FHL) is linked to mutations in the PRF1, UNC13D, STX11, and STXBP2 genes. This retrospective study analyzed 101 FHL patients in India over the past decade, finding that FHL2 and FHL3 accounted for 84% of cases. Clinical and biochemical parameters did not distinguish FHL subtypes, but perforin expression and degranulation assays were effective for diagnosis. Molecular analysis identified 76 mutations, including 39 novel ones. Survival was low (28%) regardless of mutation type or age of onset. This study highlights the genetic diversity and poor prognosis of FHL in India, emphasizing the importance of both mutational analysis and flow cytometry for diagnosis and validation of novel variants.

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.

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.

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.

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).

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].

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].

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.

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.

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.

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.

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.

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).

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.

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.

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.