title: Non-syndromic hearing impairment in India: high allelic heterogeneity among mutations in TMPRSS3, TMC1, USHIC, CDH23 and TMIE.
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.
authors.affiliation: Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India.
authors.forename: Aparna
authors.initials: A
authors.lastname: Ganapathy
authors.affiliation: Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India.
authors.forename: Nishtha
authors.initials: N
authors.lastname: Pandey
authors.affiliation: Department of Genetics, Dr. ALM Post Graduate Institute of Basic Medical Sciences, Chennai, India.
authors.forename: C R Srikumari
authors.initials: CR
authors.lastname: Srisailapathy
authors.affiliation: Department of Audiology, Ali Yavar Jung National Institute for the Hearing Handicapped, Mumbai, India.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Jalvi
authors.affiliation: Department of ENT, Maulana Azad Medical College, New Delhi, India.
authors.forename: Vikas
authors.initials: V
authors.lastname: Malhotra
authors.affiliation: Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India.
authors.forename: Mohan
authors.initials: M
authors.lastname: Venkatappa
authors.affiliation: Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India.
authors.forename: Arunima
authors.initials: A
authors.lastname: Chatterjee
authors.affiliation: Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India.
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India.
authors.forename: Rekha
authors.initials: R
authors.lastname: Santhanam
authors.affiliation: Department of ENT, Maulana Azad Medical College, New Delhi, India.
authors.forename: Shelly
authors.initials: S
authors.lastname: Chadha
authors.affiliation: Department of Genetics, Dr. ALM Post Graduate Institute of Basic Medical Sciences, Chennai, India.
authors.forename: Arabandi
authors.initials: A
authors.lastname: Ramesh
authors.affiliation: Department of ENT, Maulana Azad Medical College, New Delhi, India.
authors.forename: Arun K
authors.initials: AK
authors.lastname: Agarwal
authors.affiliation: Department of Audiology, Ali Yavar Jung National Institute for the Hearing Handicapped, Mumbai, India.
authors.forename: Raghunath R
authors.initials: RR
authors.lastname: Rangasayee
authors.affiliation: Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India.
authors.forename: Anuranjan
authors.initials: A
authors.lastname: Anand
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000483:Alleles; D000818:Animals; D001483:Base Sequence; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000235:genetics; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D005091:Exons / Q000235:genetics; D005260:Female; D034381:Hearing Loss / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007194:India; D007438:Introns / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C442480:CDH23 protein, human; D000070585:Cadherin Related Proteins; D015820:Cadherins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C451751:TMC1 protein, human; C466299:TMIE protein, human; C118970:USH1C protein, human; D012697:Serine Endopeptidases; C409042:TMPRSS3 protein, human