{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:01:41Z","timestamp":1753869701238,"version":"3.41.2"},"reference-count":20,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T00:00:00Z","timestamp":1720483200000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81960040"],"award-info":[{"award-number":["81960040"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Deafness autosomal dominant 2A (DFNA2A) is related to non\u2010syndromic genetic hearing impairment. The <jats:italic>KCNQ<\/jats:italic>4 (Potassium Voltage\u2010Gated Channel Subfamily Q Member 4) can lead to DFNA2A. In this study, we report a case of autosomal dominant non\u2010syndromic hearing loss with six family members as caused by a novel variant in the <jats:italic>KCNQ<\/jats:italic><jats:italic>4<\/jats:italic> gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The whole\u2010exome sequencing (WES) and pure tone audiometry were performed on the proband of the family. Sanger sequencing was conducted on family members to determine if the novel variant in the <jats:italic>KCNQ<\/jats:italic>4 gene was present. Evolutionary conservation analysis and computational tertiary structure protein prediction of the wild\u2010type KCNQ4 protein and its variant were then performed. In addition, voltage\u2010gated channel activity of the wild\u2010type KCNQ4 protein and its variant were tested using whole\u2010cell patch clamp.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>It was observed that the proband had inherited autosomal dominant, non\u2010syndromic sensorineural hearing loss as a trait. A novel co\u2010segregating heterozygous missense variant (c.902C&gt;A, p.Ala301Asp) of the <jats:italic>KCNQ<\/jats:italic><jats:italic>4<\/jats:italic> gene was identified in the proband and other five affected family members. This variant was predicted to cause an alanine\u2010to\u2010aspartic acid substitution at position 301 in the KCNQ4 protein. The alanine at position 301 is well conserved across different species. Whole\u2010cell patch clamp showed that there was a significant difference between the WT protein currents and the mutant protein currents in the voltage\u2010gated channel activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In the present study, performing WES in conjunction with Sanger sequencing enhanced the detection of a novel, potentially causative variant (c301 A&gt;G; p.Ala301Asp) in exon 6 of the <jats:italic>KCNQ<\/jats:italic><jats:italic>4<\/jats:italic> gene. Therefore, our findings contributed to the mutation spectrum of the <jats:italic>KCNQ<\/jats:italic><jats:italic>4<\/jats:italic> gene and may be useful in the diagnosis and gene therapy of deafness autosomal dominant 2A.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2446","type":"journal-article","created":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T18:18:48Z","timestamp":1720549128000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A novel variant c.902C&gt;A (p. A301D) in <i>KCNQ4<\/i> associated with non\u2010syndromic deafness 2A in a Chinese family"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3601-3308","authenticated-orcid":false,"given":"Lingyan","family":"Ren","sequence":"first","affiliation":[{"name":"Department of Medical Genetics\/Prenatal Diagnosis Center Guizhou Provincial People's Hospital  Guiyang Guizhou Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3940-7014","authenticated-orcid":false,"given":"Jiangfen","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics\/Prenatal Diagnosis Center Guizhou Provincial People's Hospital  Guiyang Guizhou Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Kuang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics\/Prenatal Diagnosis Center Guizhou Provincial People's Hospital  Guiyang Guizhou Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics\/Prenatal Diagnosis Center Guizhou Provincial People's Hospital  Guiyang Guizhou Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minmin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics\/Prenatal Diagnosis Center Guizhou Provincial People's Hospital  Guiyang Guizhou Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaozhen","family":"Zhuo","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics\/Prenatal Diagnosis Center Guizhou Provincial People's Hospital  Guiyang Guizhou Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zuwei","family":"Cao","sequence":"additional","affiliation":[{"name":"Center for Rehabilitative Auditory Research Guizhou Provincial People's Hospital  Guiyang Guizhou Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0394-240X","authenticated-orcid":false,"given":"Shengwen","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics\/Prenatal Diagnosis Center Guizhou Provincial People's Hospital  Guiyang Guizhou Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,7,9]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.14164"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5360.69"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.57.4.10"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10092254"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881\u2010017\u20100396\u20105"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10038\u2010006\u20100384\u20107"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0092\u20108674(00)80556\u20105"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2021.12059"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0063231"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276\u2010023\u201000976\u20104"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrep.2020.100879"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22052510"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439\u2010016\u20101648\u20108"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439\u2010021\u201002424\u20107"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0289247"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1254806"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes12111711"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.13201\/j.issn.2096\u20107993.2023.01.005"}],"container-title":["Molecular Genetics &amp; 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