{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T08:18:45Z","timestamp":1773389925634,"version":"3.50.1"},"reference-count":36,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health, Labor and Welfare of Japan","award":["20FC10148"],"award-info":[{"award-number":["20FC10148"]}]},{"name":"Ministry of Health, Labor and Welfare of Japan","award":["23FC10149"],"award-info":[{"award-number":["23FC10149"]}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["JP16kk0205010"],"award-info":[{"award-number":["JP16kk0205010"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["JP18ek0109363"],"award-info":[{"award-number":["JP18ek0109363"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["JP21ek0109542"],"award-info":[{"award-number":["JP21ek0109542"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["JP24ek0109741"],"award-info":[{"award-number":["JP24ek0109741"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: MYO7A is known to be the genetic cause of Usher syndrome type 1, as well as autosomal dominant and autosomal recessive non-syndromic hearing loss. In general, autosomal dominant MYO7A-associated hearing loss shows progressive high-frequency, sloping hearing loss. However, several variants are associated with low-frequency hearing loss. MYO7A-associated low-frequency hearing loss is relatively rare, and the clinical details remain unclear. Methods: A total of 18,475 Japanese patients with hearing loss were recruited. Targeted massively parallel sequencing of 158 deafness-related genes was performed, and individuals with variants related to MYO7A-associated low-frequency hearing loss were identified. Results: Among 18,475 hearing loss patients, we identified 60 patients from 44 unrelated families carrying five variants (p.[Asn140Lys; Glu1835Gln], p.Leu479Pro, p.Leu656Val, p.Gly660Arg, and p.Arg668His) for MYO7A-associated low-frequency hearing loss. Patients identified in this study initially showed postlingual-onset mild-to-moderate low-frequency hearing loss; however, high-frequency hearing also deteriorated after the fourth decade, eventually leading to moderate-to-severe flat-type hearing loss. In addition, we performed haplotype analysis for the recurrent variant c.1436T&gt;C:p.Leu479Pro identified in this study and found that this variant is a founder mutation in the Japanese population. Conclusions: In this study, we were able to clarify the specific features of MYO7A-related low-frequency hearing loss in a significant number of patients. In particular, we clarified the details of hearing deterioration at each frequency. Our findings will be useful for providing more appropriate treatment and follow-up for MYO7A-associated low-frequency hearing loss.<\/jats:p>","DOI":"10.3390\/genes17030314","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T10:43:27Z","timestamp":1773225807000},"page":"314","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Details of Low-Frequency Hearing Loss Observed in Autosomal Dominant MYO7A-Associated Hearing Loss Patients"],"prefix":"10.3390","volume":"17","author":[{"given":"Hiromi","family":"Koizumi","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Kyouai Hospital, Fujinomiya 418-0067, Japan"},{"name":"Department of Hearing Implant Sciences, Shinshu University School of Medicine, Matsumoto 390-8621, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6640-2297","authenticated-orcid":false,"given":"Shin-ya","family":"Nishio","sequence":"additional","affiliation":[{"name":"Department of Hearing Implant Sciences, Shinshu University School of Medicine, Matsumoto 390-8621, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5068-6122","authenticated-orcid":false,"given":"Shin-ichi","family":"Usami","sequence":"additional","affiliation":[{"name":"Department of Hearing Implant Sciences, Shinshu University School of Medicine, Matsumoto 390-8621, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/374060a0","article-title":"Defective myosin VIIA gene responsible for Usher syndrome type 1B","volume":"374","author":"Weil","year":"1995","journal-title":"Nature"},{"key":"ref_2","first-page":"1197","article-title":"Autosomal dominant non-syndromic deafness caused by a mutation in the myosin VIIA gene","volume":"1038","author":"Liu","year":"1997","journal-title":"Nat. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1038\/ng0697-188","article-title":"Mutations in the myosin VIIA gene cause non-syndromic recessive deafness","volume":"16","author":"Liu","year":"1997","journal-title":"Nat. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"9815","DOI":"10.1073\/pnas.92.21.9815","article-title":"Expression in cochlea and retina of myosin VIIa, the gene product defective in Usher syndrome type 1B","volume":"92","author":"Hasson","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6689","DOI":"10.1093\/emboj\/cdf689","article-title":"Myosin VIIa, harmonin and cadherin 23, three Usher I gene products that cooperate to shape the sensory hair cell bundle","volume":"21","author":"Bahloul","year":"2002","journal-title":"EMBO J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3557","DOI":"10.1093\/hmg\/ddq271","article-title":"Cadherin-23, myosin VIIa and harmonin, encoded by Usher syndrome type I genes, form a ternary complex and interact with membrane phospholipids","volume":"19","author":"Bahloul","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"11476","DOI":"10.1073\/pnas.1104161108","article-title":"Myosin VIIa and sans localization at stereocilia upper tip-link density implicates these Usher syndrome proteins in mechanotransduction","volume":"108","author":"Grati","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"33460","DOI":"10.1074\/jbc.M112.378505","article-title":"Large protein assemblies formed by multivalent interactions between cadherin23 and harmonin suggest a stable anchorage structure at the tip link of stereocilia","volume":"287","author":"Wu","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1016\/j.celrep.2019.09.027","article-title":"Myosin VII, USH1C, and ANKS4B or USH1G Together Form Condensed Molecular Assembly via Liquid-Liquid Phase Separation","volume":"29","author":"He","year":"2019","journal-title":"Cell Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"15864","DOI":"10.1038\/ncomms15864","article-title":"Myosin 7 and its adaptors link cadherins to actin","volume":"8","author":"Yu","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4593","DOI":"10.1242\/jcs.02636","article-title":"Usher I syndrome: Unravelling the mechanisms that underlie the cohesion of the growing hair bundle in inner ear sensory cells","volume":"118","author":"Petit","year":"2005","journal-title":"J. Cell Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e2414707122","DOI":"10.1073\/pnas.2414707122","article-title":"MYO7A is required for the functional integrity of the mechanoelectrical transduction complex in hair cells of the adult cochlea","volume":"122","author":"Underhill","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00439-013-1358-4","article-title":"The Human Gene Mutation Database: Building a comprehensive mutation repository for clinical and molecular genetics, diagnostic testing and personalized genomic medicine","volume":"133","author":"Stenson","year":"2014","journal-title":"Hum. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8326","DOI":"10.1038\/s41598-024-57415-1","article-title":"The prevalence and clinical features of MYO7A-related hearing loss including DFNA11, DFNB2 and USH1B","volume":"4","author":"Watanabe","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5962","DOI":"10.12998\/wjcc.v11.i25.5962","article-title":"Autosomal dominant non-syndromic hearing loss caused by a novel mutation in MYO7A: A case report and review of the literature","volume":"11","author":"Xia","year":"2023","journal-title":"World J. Clin. Cases"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1089\/gtmb.2014.0252","article-title":"Clinical application of a custom AmpliSeq library and ion torrent PGM sequencing to comprehensive mutation screening for deafness genes","volume":"19","author":"Nishio","year":"2015","journal-title":"Genet. Test. Mol. Biomarkers"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1093\/nar\/gkq603","article-title":"ANNOVAR: Functional annotation of genetic variants from high-throughput sequencing data","volume":"38","author":"Wang","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1002\/humu.23160","article-title":"The Clinical Next-Generation Sequencing Database: A Tool for the Unified Management of Clinical Information and Genetic Variants to Accelerate Variant Pathogenicity Classification","volume":"38","author":"Nishio","year":"2017","journal-title":"Hum. Mutat."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1002\/mgg3.399","article-title":"Simple and efficient germline copy number variant visualization method for the Ion AmpliSeq custom panel","volume":"6","author":"Nishio","year":"2018","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"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","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1002\/humu.23630","article-title":"Expert specification of the ACMG\/AMP variant interpretation guidelines for genetic hearing loss","volume":"39","author":"Oza","year":"2018","journal-title":"Hum. Mutat."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1080\/16513860301713","article-title":"Recommendations for the description of genetic and audiological data for families with nonsyndromic hereditary hearing impairment","volume":"1","author":"Mazzoli","year":"2003","journal-title":"Audiol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1097\/00005537-200202000-00017","article-title":"Phenotype of DFNA11: A nonsyndromic hearing loss caused by a myosin VIIA mutation","volume":"112","author":"Tamagawa","year":"2002","journal-title":"Laryngoscope"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10950","DOI":"10.1074\/jbc.M116.765966","article-title":"Human myosin VIIa is a very slow processive motor protein on various cellular actin structures","volume":"292","author":"Sato","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.ajhg.2018.08.006","article-title":"Genomic Landscape and Mutational Signatures of Deafness-Associated Genes","volume":"103","author":"Azaiez","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1159\/000529464","article-title":"Monogenic Causes of Low-Frequency Non-Syndromic Hearing Loss","volume":"28","author":"Gan","year":"2023","journal-title":"Audiol. Neurootol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1097\/MAO.0b013e3181825651","article-title":"In search of the DFNA11 myosin VIIA low- and mid-frequency auditory genetic modifier","volume":"29","author":"Kallman","year":"2008","journal-title":"Otol. Neurotol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kobayashi, M., Miyagawa, M., Nishio, S.Y., Moteki, H., Fujikawa, T., Ohyama, K., Sakaguchi, H., Miyanohara, I., Sugaya, A., and Naito, Y. (2018). WFS1 mutation screening in a large series of Japanese hearing loss patients Massively parallel DNA sequencing-based analysis. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0193359"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1186\/s12967-015-0624-8","article-title":"Strong founder effect of p. P240L in CDH23 in Koreans and its significant contribution to severe-to-profound nonsyndromic hearing loss in a Korean pediatric population","volume":"13","author":"Kim","year":"2015","journal-title":"J. Trans. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/jhg.2016.120","article-title":"A novel founder MYO15A frameshift duplication is the major cause of genetic hearing loss in Oman","volume":"62","author":"Palombo","year":"2017","journal-title":"J. Hum. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1002\/ajmg.b.32774","article-title":"Identification of TMC1 as a relatively common cause for nonsyndromic hearing loss in the Saudi population","volume":"183","author":"Ramzan","year":"2020","journal-title":"Am. J. Med. Genet. B Neuropsychiatr. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1111\/j.1399-0004.2012.01897.x","article-title":"A prevalent founder mutation and genotype-phenotype correlations of OTOF in Japanese patients with auditory neuropathy","volume":"82","author":"Matsunaga","year":"2012","journal-title":"Clin. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Naito, T., Nishio, S.Y., Iwasa, Y., Yano, T., Kumakawa, K., Abe, S., Ishikawa, K., Kojima, H., Namba, A., and Oshikawa, C. (2013). Comprehensive genetic screening of KCNQ4 in a large autosomal dominant nonsyndromic hearing loss cohort: Genotype-phenotype correlations and a founder mutation. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063231"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Maekawa, K., Nishio, S.Y., Abe, S., Goto, S.I., Honkura, Y., Iwasaki, S., Kanda, Y., Kobayashi, Y., Oka, S.I., and Okami, M. (2019). Mutational spectrum and clinical features of patients with LOXHD1 variants identified in an 8074 hearing loss patient cohort. Genes, 10.","DOI":"10.3390\/genes10100735"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Yasukawa, R., Moteki, H., Nishio, S.Y., Ishikawa, K., Abe, S., Honkura, Y., Hyogo, M., Mihashi, R., Ikezono, T., and Shintani, T. (2019). The prevalence and clinical characteristics of TECTA-associated autosomal dominant hearing loss. Genes, 10.","DOI":"10.3390\/genes10100744"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41586-023-06045-0","article-title":"A genomic mutational constraint map using variation in 76,156 human genomes","volume":"625","author":"Chen","year":"2024","journal-title":"Nature"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/3\/314\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T05:34:12Z","timestamp":1773380052000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/3\/314"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,11]]},"references-count":36,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["genes17030314"],"URL":"https:\/\/doi.org\/10.3390\/genes17030314","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,11]]}}}