Genomic Analysis of Indian Congenital Muscular Disorder Patients Reveals a Wide Spectrum of Known and Novel Mutations

Congenital muscular dystrophies (CMD) and congenital myopathies (CM) are a group of heterogeneous degenerative primary muscle disorders. Due to vast heterogeneity, accurate diagnosis and subsequent treatment can present considerable challenges. Therefore, it is necessary to acquire a complete knowledge of the genomic signatures of the various subtypes of these disorders. In the current study, using whole exome sequencing (WES), in a cohort of 36 phenotypically well-characterized CM and CMD patients from India, we have identified rare and deleterious mutations in reported as well as novel genes by applying stringent filtering criteria using multiple bioinformatics tools and databases. We also investigated the complex genotype-phenotype relationship in order to reach a final diagnosis in 38% (8 of 21) CMD and 40% (6 of 15) CM patients. Furthermore, using in silico pathway enrichment analysis, we were able to identify a number of significant pathways that might have a role towards disease pathogenesis. Taken together, our analysis has produced a rich source of genetic data underlying CMD and CM in India, which will be invaluable for further elucidation of the biological basis of these disorders.