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

Sarcoglycanopathies are autosomal recessive limb-girdle muscular dystrophies (LGMDs) caused by mutations in genes encoding the α, β, γ, and δ proteins that stabilize the muscle cell sarcolemma. Clinically, they present as progressive proximal muscle weakness with childhood onset. Muscle biopsy confirms dystrophic changes and sarcoglycan protein deficiencies. This study summarized 1,046 LGMD patients diagnosed via targeted sequencing. The most frequent phenotypes were LGMDR1 (19.7%), LGMDR4 (19.0%), LGMDR2 (17.5%), and MMD1 (14.5%). Variants in CAPN3, SGCB, and DYSF were found in over 10% of patients, with SGCB p.Thr182Pro being the most common (12.5%), homozygous in 97.9%. Genotyping of 68 patients with this variant revealed a ~1 Mb region of homozygosity, suggesting a shared founder effect. Five markers were significantly enriched in patients compared to controls, and admixture analysis indicated a higher proportion of West Eurasian/European ancestry. Further systematic study is needed to identify the communities and regions where the SGCB p.Thr182Pro variant is observed in higher proportions.

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