Clinical and Genomic Evaluation of 207 Genetic Myopathies in the Indian Subcontinent

• DOI: 10.3389/fneur.2020.559327
• Publication Date: 2020-11-05T08:59:47Z
• Authors: Samya Chakravorty; Babi Ramesh Reddy...; Satish Vasant Kha...; Madhu Bala Singla; Ashish Bhutada; Rashna Dastur; Pradnya Satish Ga...; Laura E Rufibach; Logan Gloster; Madhuri Hegde
• Keywords: Indian subcontinent

Objective: Inherited myopathies comprise more than 200 different individually rare disease-subtypes, but when combined together they have a high prevalence of 1 in 6,000 individuals across the world. Our goal was to determine for first time clinical- and gene-variant spectrum genetic substantial cohort study Indian subcontinent. Methods: In this study, we performed large clinical exome sequencing (ES) with phenotype correlation on 207 clinically well-characterized inherited myopathy-suspected patients from subcontinent diverse ethnicities. Results: Clinical-correlation driven definitive molecular diagnosis established 49% (101 cases; 95% CI, 42-56%) major contributing pathogenicity either three genes, GNE (28%; GNE-myopathy), DYSF (25%; Dysferlinopathy), CAPN3 (19%; Calpainopathy). We identified 65 variant alleles comprising 37 unique variants these genes. Seventy-eight percent were homozygous detected pathogenic variant, suggesting need carrier-testing autosomal-recessive disorders like Dysferlinopathy that are common India. describe observed including uncommon subtypes India: Sarcoglycanopathies (SGCA/B/D/G), Collagenopathy (COL6A1/2/3), Anoctaminopathy (ANO5), telethoninopathy (TCAP), Pompe-disease (GAA), Myoadenylate-deaminase-deficiency-myopathy (AMPD1), myotilinopathy (MYOT), laminopathy (LMNA), HSP40-proteinopathy (DNAJB6), Emery-Dreifuss-muscular-dystrophy (EMD), Filaminopathy (FLNC), TRIM32-proteinopathy (TRIM32), POMT1-proteinopathy (POMT1), Merosin-deficiency-congenital-muscular-dystrophy-type-1 (LAMA2). Thirteen harbored >1 gene had unusual features possible role synergistic-heterozygosity/digenic-contribution disease presentation progression. Conclusions: Application correlated ES myopathy has improved our understanding their overlaps patients. This, turn, will enhance global gene-variant-disease databases by data developing countries/continents efficient diagnostics.