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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Alleles*
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Animals
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Base Sequence
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Cadherin Related Proteins
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Cadherins / genetics
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Cell Cycle Proteins
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Cytoskeletal Proteins
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Exons / genetics
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Female
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Hearing Loss / genetics*
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Heterozygote
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Homozygote
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Humans
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India
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Introns / genetics
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Male
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Membrane Proteins / genetics
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Mutation*
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Neoplasm Proteins / genetics
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Serine Endopeptidases / genetics
Substances
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Adaptor Proteins, Signal Transducing
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CDH23 protein, human
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Cadherin Related Proteins
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Cadherins
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Cell Cycle Proteins
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Cytoskeletal Proteins
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Membrane Proteins
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Neoplasm Proteins
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TMC1 protein, human
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TMIE protein, human
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USH1C protein, human
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Serine Endopeptidases
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TMPRSS3 protein, human
Grants and funding
Funds for this work were provided by Department of Biotechnology, New Delhi (BT/PR4449/Med/12/172/2003) and JNCASR, Bangalore. AG and NP received research fellowships from Council of Scientific and Industrial Research, New Delhi. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.