Novel OTOF pathogenic variant segregating with non-syndromic hearing loss in a consanguineous family from tribal Rajouri in Jammu and Kashmir

Hereditary hearing loss is characterized by a very high genetic heterogeneity. The OTOF (Locus: DFNB9), encoding otoferlin, is reported to be one of the major causes of non-syndromic hearing loss, and is also reported to be the most common cause of non-syndromic recessive auditory neuropathy spectrum disorder. In this study, whole exome sequencing was employed for detection of novel pathogenic variant that segregates with autosomal recessive nonsyndromic hearing loss in a tribal family from Rajouri, Jammu and Kashmir. Proband was a 9-year-old male born to first-cousin parents and presented with sensorineural hearing loss since birth. Family resides in an area with high consanguinity and lack of basic health care facilities including genetic counselling services. We report a novel OTOF pathogenic variant NM_194248.2:c.4249_4250insG (p.Ser1417CysfsTer4) co-segregating with hearing loss in this family and not present in any public databases. Our findings not only extend the geographical and mutational spectrum of autosomal recessive nonsyndromic hearing loss but also support the need for introducing genetic counselling services to rural and tribal areas in India with high consanguinity.