Hearing loss is one of the most common sensory disorder and approximately 466 million people have disabling hearing loss worldwide. This study was conducted to identify the mutations in the GJB2, GJB3, and GJB6 genes in an Indian cohort with non-syndromic sensorineural hearing loss and ascertain its use for genetic testing. 31 affected individuals with prelingual bilateral non-syndromic severe to profound sensorineural hearing loss were identified based on clinical evaluation and audiometric assessment. Sanger Sequencing method was used. Six out of 31 affected individuals showed pathogenic nonsense mutations in GJB2 gene, accounting to 19.3%. Of the 6 affected individuals, 5 were homozygous for c.71G>A(p.Trp24Ter) and one was compound heterozygous for c.71G>A and c.370C>T(p.Gln124Ter). Missense mutations [c.380G>A(p.Arg127His) and c.457G>A(p.Val153Ile)], and 3' UTR variations were also identified in GJB2 gene. GJB3 and GJB6 genes showed only silent mutations and 3' UTR variations. 19.3% of affected individuals showing pathogenic mutations in GJB2 gene in our cohort is comparable to other Indian studies (approximately 20%) and it is less as compared to Caucasian, Japanese, and Chinese studies (approximately 50%). Lower occurrence of pathogenic mutations in GJB2 gene in our cohort and other Indian studies as compared to other Caucasian, Japanese and Chinese studies, and absence of pathogenic mutations in GJB3 and GJB6 genes indicates that these genes may have a limited role in the Indian population. Hence there is a need to identify genes that play a major role in the Indian population so that they can be used for genetic testing for NHSL to aid in accurate and early diagnosis.
Novel, Compound Heterozygous, Single-Nucleotide Variants inMARS2Associated with Developmental Delay, Poor Growth, and Sensorineural Hearing Loss