{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T15:17:34Z","timestamp":1788621454344,"version":"build-2803163510"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"3-4","license":[{"start":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T00:00:00Z","timestamp":1631577600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T00:00:00Z","timestamp":1631577600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["17kk0205010h0002"],"award-info":[{"award-number":["17kk0205010h0002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["18ek0109363h0001"],"award-info":[{"award-number":["18ek0109363h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","award":["20FC1048"],"award-info":[{"award-number":["20FC1048"]}],"id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Hum Genet"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>TMC1<\/jats:italic>\n                    is a causative gene for both autosomal dominant non-syndromic hearing loss (DFNA36) and autosomal recessive non-syndromic hearing loss (DFNB7\/11). To date, 125 pathogenic variants in\n                    <jats:italic>TMC1<\/jats:italic>\n                    have been reported. Most of the\n                    <jats:italic>TMC1<\/jats:italic>\n                    variants are responsible for autosomal recessive hearing loss, with only 8 variants reported as causative for DFNA36. Here, we reported the prevalence of\n                    <jats:italic>TMC1<\/jats:italic>\n                    -associated hearing loss in a large non-syndromic hearing loss cohort of about 12,000 subjects. As a result, we identified 26 probands with\n                    <jats:italic>TMC1<\/jats:italic>\n                    -associated hearing loss, with the estimated prevalence of\n                    <jats:italic>TMC1<\/jats:italic>\n                    -associated hearing loss in the Japanese hearing loss cohort being 0.17% among all patients. Among the 26 probands with\n                    <jats:italic>TMC1<\/jats:italic>\n                    -associated hearing loss, 15 cases were identified from autosomal dominant hearing loss families. Based on the audiometric data from the probands, family members and previously reported cases, we evaluated hearing deterioration for DFNA36 patients. In addition, we performed haplotype analysis for 11 unrelated autosomal dominant hearing loss families carrying the same variant\n                    <jats:italic>TMC1<\/jats:italic>\n                    : NM_138691:c.1627G\u2009&gt;\u2009A:p.Asp543Asn. The results clearly indicated that the same haplotype was present despite\u00a0the families being unrelated, supporting the contention that this variant occurred by founder mutation.\n                  <\/jats:p>","DOI":"10.1007\/s00439-021-02364-2","type":"journal-article","created":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T12:02:55Z","timestamp":1631620975000},"page":"929-937","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Prevalence and clinical features of autosomal dominant and recessive TMC1-associated hearing loss"],"prefix":"10.1007","volume":"141","author":[{"given":"Shin-ya","family":"Nishio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5068-6122","authenticated-orcid":false,"given":"Shin-ichi","family":"Usami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,14]]},"reference":[{"key":"2364_CR1","doi-asserted-by":"crossref","first-page":"20070","DOI":"10.1073\/pnas.2009628117","volume":"117","author":"A Abu Rayyan","year":"2020","unstructured":"Abu Rayyan A, Kamal L, Casadei S et al (2020) Genomic analysis of inherited hearing loss in the Palestinian population. Proc Natl Acad Sci USA 117:20070\u201320076","journal-title":"Proc Natl Acad Sci USA"},{"key":"2364_CR2","doi-asserted-by":"publisher","first-page":"295ra108","DOI":"10.1126\/scitranslmed.aab1996","volume":"7","author":"C Askew","year":"2015","unstructured":"Askew C, Rochat C, Pan B et al (2015) Tmc gene therapy restores auditory function in deaf mice. Sci Transl Med. 7:295ra108","journal-title":"Sci Transl Med."},{"key":"2364_CR3","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1016\/j.ajhg.2018.08.006","volume":"103","author":"H Azaiez","year":"2018","unstructured":"Azaiez H, Booth KT, Ephraim SS et al (2018) Genomic landscape and mutational signatures of deafness-associated genes. Am J Hum Genet 103:484\u2013497","journal-title":"Am J Hum Genet"},{"key":"2364_CR37","doi-asserted-by":"crossref","unstructured":"Brownstein Z, Gulsuner S, Walsh T et al (2020) Spectrum of genes for inherited hearing loss in the Israeli Jewish population, including the novel human deafness gene ATOH1. Clin Genet 98:353\u2013364","DOI":"10.1111\/cge.13817"},{"key":"2364_CR4","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1038\/nature25164","volume":"553","author":"X Gao","year":"2018","unstructured":"Gao X, Tao Y, Lamas V et al (2018) Treatment of autosomal dominant hearing loss by in vivo delivery of genome editing agents. Nature 553:217\u2013221","journal-title":"Nature"},{"key":"2364_CR5","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1038\/s41591-019-0500-9","volume":"25","author":"B Gy\u00f6rgy","year":"2019","unstructured":"Gy\u00f6rgy B, Nist-Lund C, Pan B et al (2019) Allele-specific gene editing prevents deafness in a model of dominant progressive hearing loss. Nat Med 25:1123\u20131130","journal-title":"Nat Med"},{"key":"2364_CR6","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1007\/s13353-014-0263-4","volume":"56","author":"MA Hassan","year":"2015","unstructured":"Hassan MA, Shah AA, Szmida E et al (2015) A TMC1 (transmembrane channel-like 1) mutation (p. S320R) in a Polish family with hearing impairment. J Appl Genet 56:311\u2013316","journal-title":"J Appl Genet"},{"key":"2364_CR7","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1080\/16513860310003049","volume":"1","author":"PLM Huygen","year":"2003","unstructured":"Huygen PLM, Pennings RJE, Cremers CWRJ (2003) Characterizing and distinguishing progressive phenotypes in nonsyndromic autosomal dominant hearing impairment. Audiol Med 1:37\u201346","journal-title":"Audiol Med"},{"key":"2364_CR8","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1002\/humu.9384","volume":"26","author":"E Kalay","year":"2005","unstructured":"Kalay E, Karaguzel A, Caylan R et al (2005) Four novel TMC1 (DFNB7\/DFNB11) mutations in Turkish patients with congenital autosomal recessive nonsyndromic hearing loss. Hum Mutat 26:591","journal-title":"Hum Mutat"},{"key":"2364_CR9","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1111\/j.1399-0004.2007.00739.x","volume":"71","author":"S Kitajiri","year":"2007","unstructured":"Kitajiri S, Makishima T, Friedman TB, Griffith AJ (2007a) A novel mutation at the DFNA36 hearing loss locus reveals a critical function and potential genotype-phenotype correlation for amino acid-572 of TMC1. Clin Genet 71:148\u2013152","journal-title":"Clin Genet"},{"key":"2364_CR10","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1111\/j.1399-0004.2007.00895.x","volume":"72","author":"SI Kitajiri","year":"2007","unstructured":"Kitajiri SI, McNamara R, Makishima T et al (2007b) Identities, frequencies and origins of TMC1 mutations causing DFNB7\/B11 deafness in Pakistan. Clin Genet 72:546\u2013550","journal-title":"Clin Genet"},{"key":"2364_CR11","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1038\/ng842","volume":"30","author":"K Kurima","year":"2002","unstructured":"Kurima K, Peters LM, Yang Y et al (2002) Dominant and recessive deafness caused by mutations of a novel gene, TMC1, required for cochlear hair-cell function. Nat Genet 30:277\u2013284","journal-title":"Nat Genet"},{"key":"2364_CR12","doi-asserted-by":"publisher","first-page":"e0188578","DOI":"10.1371\/journal.pone.0188578","volume":"13","author":"T Likar","year":"2018","unstructured":"Likar T, Hasanhod\u017ei\u0107 M, Teran N et al (2018) Diagnostic outcomes of exome sequencing in patients with syndromic or non-syndromic hearing loss. PLoS ONE 13:e0188578","journal-title":"PLoS ONE"},{"key":"2364_CR13","doi-asserted-by":"crossref","unstructured":"Liu S, Wang S, Zou L, Xiong W (2020) Mechanisms in cochlear hair cell mechano-electrical transduction for acquisition of sound frequency and intensity. Cell Mol Life Sci. Online ahead of print","DOI":"10.1007\/s00018-021-03840-8"},{"issue":"1","key":"2364_CR38","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1002\/humu.9302","volume":"25","author":"Christian G. Meyer","year":"2005","unstructured":"Meyer CG, Gasmelseed NM, Mergani A et al (2005) Novel TMC1 structural and splice variants associated with congenital nonsyndromic deafness in a Sudanese pedigree. Hum Mutat 25:100","journal-title":"Human Mutation"},{"key":"2364_CR14","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1111\/cge.12677","volume":"89","author":"H Moteki","year":"2016","unstructured":"Moteki H, Azaiez H, Booth KT et al (2016) Comprehensive genetic testing with ethnic-specific filtering by allele frequency in a Japanese hearing-loss population. Clin Genet 89:466\u2013472","journal-title":"Clin Genet"},{"key":"2364_CR15","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1002\/humu.23160","volume":"38","author":"SY Nishio","year":"2017","unstructured":"Nishio SY, Usami SI (2017) The clinical next-generation sequencing database: a tool for the unified management of clinical information and genetic variants to accelerate variant pathogenicity classification. Hum Mutat 38:252\u2013259","journal-title":"Hum Mutat"},{"key":"2364_CR16","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1089\/gtmb.2014.0252","volume":"19","author":"SY Nishio","year":"2015","unstructured":"Nishio SY, Hayashi Y, Watanabe M, Usami S (2015) Clinical application of a custom AmpliSeq library and ion torrent PGM sequencing to comprehensive mutation screening for deafness genes. Genet Test Mol Biomarkers 19:209\u2013217","journal-title":"Genet Test Mol Biomarkers"},{"key":"2364_CR17","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1038\/s41467-018-08264-w","volume":"10","author":"CA Nist-Lund","year":"2019","unstructured":"Nist-Lund CA, Pan B, Patterson A et al (2019) Improved TMC1 gene therapy restores hearing and balance in mice with genetic inner ear disorders. Nat Commun 10:236","journal-title":"Nat Commun"},{"key":"2364_CR18","doi-asserted-by":"publisher","first-page":"1593","DOI":"10.1002\/humu.23630","volume":"39","author":"AM Oza","year":"2018","unstructured":"Oza AM, DiStefano MT, Hemphill SE et al (2018) Expert specification of the ACMG\/AMP variant interpretation guidelines for genetic hearing loss. Hum Mutat 39:1593\u20131613","journal-title":"Hum Mutat"},{"key":"2364_CR19","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1002\/ajmg.b.32774","volume":"183","author":"K Ramzan","year":"2020","unstructured":"Ramzan K, Al-Owain M, Al-Numair NS et al (2020) Identification of TMC1 as a relatively common cause for nonsyndromic hearing loss in the Saudi population. Am J Med Genet B Neuropsychiatr Genet 183:172\u2013180","journal-title":"Am J Med Genet B Neuropsychiatr Genet"},{"key":"2364_CR20","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards S, Aziz N, Bale S et al (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17:405\u2013424","journal-title":"Genet Med"},{"key":"2364_CR21","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1111\/cge.13839","volume":"98","author":"D Safka Brozkova","year":"2020","unstructured":"Safka Brozkova D, Poisson Markov\u00e1 S, M\u00e9sz\u00e1rosov\u00e1 AU et al (2020) Spectrum and frequencies of non GJB2 gene mutations in Czech patients with early non-syndromic hearing loss detected by gene panel NGS and whole-exome sequencing. Clin Genet 98:548\u2013554","journal-title":"Clin Genet"},{"key":"2364_CR22","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1038\/ejhg.2016.182","volume":"25","author":"CZ Seco","year":"2017","unstructured":"Seco CZ, Wesdorp M, Feenstra I et al (2017) The diagnostic yield of whole-exome sequencing targeting a gene panel for hearing impairment in The Netherlands. Eur J Hum Genet 25:308\u2013314","journal-title":"Eur J Hum Genet"},{"key":"2364_CR23","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1016\/j.ajhg.2016.03.028","volume":"98","author":"SB Shibata","year":"2016","unstructured":"Shibata SB, Ranum PT, Moteki H et al (2016) RNA interference prevents autosomal-dominant hearing loss. Am J Hum Genet 98:1101\u20131113","journal-title":"Am J Hum Genet"},{"key":"2364_CR24","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1016\/j.ijporl.2009.01.005","volume":"73","author":"A Sirmaci","year":"2009","unstructured":"Sirmaci A, Duman D, Ozt\u00fcrkmen-Akay H et al (2009) Mutations in TMC1 contribute significantly to nonsyndromic autosomal recessive sensorineural hearing loss: a report of five novel mutations. Int J Pediatr Otorhinolaryngol 73:699\u2013705","journal-title":"Int J Pediatr Otorhinolaryngol"},{"key":"2364_CR25","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1007\/s00439-016-1648-8","volume":"135","author":"CM Sloan-Heggen","year":"2016","unstructured":"Sloan-Heggen CM, Bierer AO, Shearer AE et al (2016) Comprehensive genetic testing in the clinical evaluation of 1119 patients with hearing loss. Hum Genet 135:441\u2013450","journal-title":"Hum Genet"},{"key":"2364_CR26","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1002\/humu.22999","volume":"37","author":"M Sommen","year":"2016","unstructured":"Sommen M, Schrauwen I, Vandeweyer G et al (2016) DNA diagnostics of hereditary hearing loss: a targeted resequencing approach combined with a mutation classification system. Hum Mutat 37:812\u2013819","journal-title":"Hum Mutat"},{"key":"2364_CR27","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1159\/000115430","volume":"13","author":"A Tlili","year":"2008","unstructured":"Tlili A, Rebeh IB, Aifa-Hmani M et al (2008) TMC1 but not TMC2 is responsible for autosomal recessive nonsyndromic hearing impairment in Tunisian families. Audiol Neurootol 13:213\u2013218","journal-title":"Audiol Neurootol"},{"key":"2364_CR28","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1038\/ng848","volume":"30","author":"S Vreugde","year":"2002","unstructured":"Vreugde S, Erven A, Kros CJ et al (2002) Beethoven, a mouse model for dominant, progressive hearing loss DFNA36. Nat Genet 30:257\u2013258","journal-title":"Nat Genet"},{"key":"2364_CR29","doi-asserted-by":"publisher","first-page":"e164","DOI":"10.1093\/nar\/gkq603","volume":"38","author":"K Wang","year":"2010","unstructured":"Wang K, Li M, Hakonarson H (2010) ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res 38:e164","journal-title":"Nucleic Acids Res"},{"key":"2364_CR30","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1002\/mgg3.394","volume":"6","author":"H Wang","year":"2018","unstructured":"Wang H, Wu K, Guan J et al (2018) Identification of four TMC1 variations in different Chinese families with hereditary hearing loss. Mol Genet Genomic Med 6:504\u2013513","journal-title":"Mol Genet Genomic Med"},{"key":"2364_CR31","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1016\/j.ymthe.2020.11.016","volume":"29","author":"J Wu","year":"2021","unstructured":"Wu J, Solanes P, Nist-Lund C et al (2021) Single and dual vector gene therapy with AAV9-PHP.B rescues hearing in Tmc1 mutant mice. Mol Ther 29:973\u2013988","journal-title":"Mol Ther"},{"key":"2364_CR32","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1111\/j.1399-0004.2009.01338.x","volume":"77","author":"T Yang","year":"2010","unstructured":"Yang T, Kahrizi K, Bazazzadeghan N et al (2010) A novel mutation adjacent to the Bth mouse mutation in the TMC1 gene makes this mouse an excellent model of human deafness at the DFNA36 locus. Clin Genet 77:395\u2013398","journal-title":"Clin Genet"},{"key":"2364_CR33","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1186\/1750-1172-8-85","volume":"8","author":"T Yang","year":"2013","unstructured":"Yang T, Wei X, Chai Y et al (2013) Genetic etiology study of the non-syndromic deafness in Chinese Hans by targeted next-generation sequencing. Orphanet J Rare Dis 8:85","journal-title":"Orphanet J Rare Dis"},{"key":"2364_CR34","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1016\/j.ymthe.2018.12.014","volume":"27","author":"H Yoshimura","year":"2019","unstructured":"Yoshimura H, Shibata SB, Ranum PT et al (2019) Targeted allele suppression prevents progressive hearing loss in the mature Murine model of Human TMC1 deafness. Mol Ther 27:681\u2013690","journal-title":"Mol Ther"},{"key":"2364_CR35","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1038\/s41431-019-0510-6","volume":"28","author":"Y Yuan","year":"2020","unstructured":"Yuan Y, Li Q, Su Y et al (2020) Comprehensive genetic testing of Chinese SNHL patients and variants interpretation using ACMG guidelines and ethnically matched normal controls. Eur J Hum Genet 28:231\u2013243","journal-title":"Eur J Hum Genet"},{"key":"2364_CR36","doi-asserted-by":"publisher","first-page":"e97064","DOI":"10.1371\/journal.pone.0097064","volume":"9","author":"Y Zhao","year":"2014","unstructured":"Zhao Y, Wang D, Zong L et al (2014) A novel DFNA36 mutation in TMC1 orthologous to the Beethoven (Bth) mouse associated with autosomal dominant hearing loss in a Chinese family. PLoS ONE 9:e97064","journal-title":"PLoS ONE"}],"container-title":["Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00439-021-02364-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00439-021-02364-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00439-021-02364-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,23]],"date-time":"2022-04-23T03:07:16Z","timestamp":1650683236000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00439-021-02364-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,14]]},"references-count":38,"journal-issue":{"issue":"3-4","published-print":{"date-parts":[[2022,4]]}},"alternative-id":["2364"],"URL":"https:\/\/doi.org\/10.1007\/s00439-021-02364-2","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-581891\/v1","asserted-by":"object"}]},"ISSN":["0340-6717","1432-1203"],"issn-type":[{"value":"0340-6717","type":"print"},{"value":"1432-1203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,14]]},"assertion":[{"value":"31 May 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 September 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 September 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All authors declare no conflicts of interest in this study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}