Abstract
Mutations in the autosomal genes TMPRSS3, TMC1, USHIC, CDH23 and TMIE are known to cause hereditary hearing loss. To study the contribution of these genes to autosomal recessive, non-syndromic hearing loss (ARNSHL) in India, we examined 374 families with the disorder to identify potential mutations. We found four mutations in TMPRSS3, eight in TMC1, ten in USHIC, eight in CDH23 and three in TMIE. Of the 33 potentially pathogenic variants identified in these genes, 23 were new and the remaining have been previously reported. Collectively, mutations in these five genes contribute to about one-tenth of ARNSHL among the families examined. New mutations detected in this study extend the allelic heterogeneity of the genes and provide several additional variants for structure-function correlation studies. These findings have implications for early DNA-based detection of deafness and genetic counseling of affected families in the Indian subcontinent.
Highlights
Hearing impairment is the most common sensory defect in humans, occurring at a frequency of about one in 1000 live births, of which 50% are due to genetic causes [1]
We describe the spectrum of mutations in TMPRSS3, TMC1, USHIC, CDH23 and TMIE in 374 families with ARNSHL from India
The possibility for mutation could not be excluded in 48 families for TMPRSS3, in 50 families for TMC1, in 24 families for CDH23 and in 46 families for USH1C
Summary
Hearing impairment is the most common sensory defect in humans, occurring at a frequency of about one in 1000 live births, of which 50% are due to genetic causes [1]. About 70% of hereditary hearing loss is non-syndromic, wherein hearing impairment is not associated with any additional clinical phenotype. 65 genes for non-syndromic hearing loss (NSHL) have been identified (http://hereditaryhearingloss.org/) [2]. Mutations in TMPRSS3 (transmembrane serine protease 3) [3], TMC1 (transmembrane cochlear-expressed gene 1) [4], USHIC (Usher 1C) [5], CDH23 (cadherin 23) [6] and TMIE (transmembrane inner ear) [7] are known to play a causative role in NSHL. TMPRSS3 [3], TMC1 [4] and TMIE [7], were identified in studies involving a few multi-affected families from the Indian subcontinent. We describe the spectrum of mutations in TMPRSS3, TMC1, USHIC, CDH23 and TMIE in 374 families with ARNSHL from India
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