Whole-exome analyses of congenital non-syndromic deafness to understand a high-resolution genomic architecture in Indian population

Deafness is one of the most common sensory disorders in humans, affecting 1 in 1000 neonates, of which more than 50% are due to genetic reasons. Inability to hear not only affects development of speech and language, but cognitive and psychosocial abilities too. It compromises social, emotional, educational, and vocational aspects of life. While we have a large genetically deaf population in India, our knowledge about the specific causes of the disorder is almost non-existent. In this study, we have included 43 NSHL probands after clinically audiological characterization. Using variant calling and stringent variant filtration criteria, whole-exome sequencing was performed to identify pathogenic mutations in previously NSHL-reported genes. Subsequently, segregation analyses were conducted in their available family trios. Consequently, in silico homology modelling and molecular dynamics simulations studies were undertaken for a number of novel and missense variants. A major emphasis of this study was to provide genetic testing and counselling to families where a specific deafness-causing mutation was detected. Additionally, the clinical and genetics communities will receive the information through this study and use this knowledge to enhance the quality of their services for deaf individuals.