Genetic and phenotypic heterogeneity in PNPT1, MYO15A, PTPRQ and SLC12A2 variants detected among hearing impaired assortative mating families in Southern India

Exome analysis was used to resolve the etiology of hearing loss (HL) in four South Indian assortative mating families. Six variants, including three novel ones, were identified in four genes: PNPT1 p.Ala46Gly and p.Asn540Ser, MYO15A p.Leu1485Pro and p.Tyr1891*, PTPRQ p.Gln1336*, and SLC12A2 p.Pro988Ser. Compound heterozygous PNPT1 variants were associated with prelingual profound sensorineural hearing loss (SNHL), vestibular dysfunction and unilateral progressive vision loss in one family. In the second family, MYO15A variants in the myosin motor domain, including a novel variant, were found to be associated with prelingual profound SNHL. A novel PTPRQ variant was associated with postlingual progressive sensorineural/mixed HL and vestibular dysfunction in the third family, with mastoid bone hypopneumatization observed in one family member. In the fourth family, the SLC12A2 novel variant was found to segregate with severe-to-profound HL causing DFNA78, across three generations. Our results suggest a high level of allelic, genotypic and phenotypic heterogeneity of HL in these families. This study is the first to report the association of PNPT1, PTPRQ and SLC12A2 variants with HL in the Indian population.