{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:08:34Z","timestamp":1772168914938,"version":"3.50.1"},"update-to":[{"DOI":"10.12688\/f1000research.27739.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T00:00:00Z","timestamp":1629763200000}}],"reference-count":20,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T00:00:00Z","timestamp":1629763200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81471430, 81773159"],"award-info":[{"award-number":["81471430, 81773159"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"\n Background:<\/ns3:bold>\n We examined the genetic variants of a Chinese family with a 22-month-old infant with sporadic non-syndromic sensorineural hearing loss (NSHL).\n <\/ns3:p>\n \n Methods:<\/ns3:bold>\n The whole-exome sequence data in the family, especially the\n de novo<\/ns3:italic>\n \n variants presented in the patient, were analyzed and the effect of the disease-causing genetic variants on the protein expression level and cellular localization were examined by cell-based functional assay.\n <\/ns3:p>\n \n Results:<\/ns3:bold>\n The infant had no known NSHL-causing variants, except two compound heterozygous variants in connexin26 gene\n GJB2<\/ns3:italic>\n ; one was the c.79G>A, c.341A>G haplotype from the asymptomatic mother who was benign, and the other was a\n de novo<\/ns3:italic>\n pathogenic c.262G>C (p.A88P).\n In vitro<\/ns3:italic>\n ,\n GJB2<\/ns3:italic>\n with\n \n c.262G>C was weakly expressed and displayed a punctate distribution in the cytoplasm and cytomembrane, while wild type\n GJB2<\/ns3:italic>\n was robustly expressed in the cytomembrane. We deduced that the\n de novo<\/ns3:italic>\n pathogenic\n GJB2<\/ns3:italic>\n c.262G>C exacerbated loss-of-function in the context of leaky variants\n \n c.79G>A, c.341A>G in the patient. Interestingly, further analysis of exome sequences revealed that the occurrence of\n de novo<\/ns3:italic>\n pathogenic variants in the infant was frequent. Among the total~47,000 variants, 143 were\n de novo<\/ns3:italic>\n in the patient, whereas among all 74 variants predicted to be pathogenic\/likely pathogenic, 21 were heterozygous and two were homozygous\n de novo<\/ns3:italic>\n . The occurrence rate of\n de novo<\/ns3:italic>\n deleterious variants was much higher (31.1%, 23\/74) than that in total (0.34%, 143\/47,000). It is notable that most genes with\n de novo<\/ns3:italic>\n deleterious variants were environment-sensitive, such as\n GJB2<\/ns3:italic>\n ,\n MNK1<\/ns3:italic>\n ,\n MNK2, MUC4<\/ns3:italic>\n ,\n RAD21<\/ns3:italic>\n and DNA copy number variations.\n <\/ns3:p>\n \n Conclusions:<\/ns3:bold>\n The full picture of genetic variants in the exome might help us to interpret the NSHL-causing variants. More research is needed into the causes of\n de novo<\/ns3:italic>\n deleterious variants and gene-environment interactions in congenital NSHL.\n <\/ns3:p>","DOI":"10.12688\/f1000research.27739.2","type":"journal-article","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T12:05:15Z","timestamp":1629806715000},"page":"61","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Whole-exome sequencing of de novo genetic variants in a Chinese family with a sporadic case of congenital nonsyndromic hearing loss"],"prefix":"10.12688","volume":"10","author":[{"given":"Sijing","family":"Hu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunqiang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingjing","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7023-3510","authenticated-orcid":false,"given":"Shunyao","family":"Liao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2021,8,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"101-118","DOI":"10.1007\/BF00186783","article-title":"Gap junctions in the rat cochlea: immunohistochemical and ultrastructural analysis.","volume":"191","author":"T Kikuchi","year":"1995","journal-title":"AnatEmbryol (Berl)"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"427-432","DOI":"10.1038\/sj.ejhg.5200826","article-title":"Connexin 26 mutations in cases of sensorineural deafness in eastern Austria.","volume":"10","author":"K Frei","year":"2002","journal-title":"Eur J Hum Genet"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"250-254","DOI":"10.1016\/j.ijporl.2009.11.014","article-title":"Prevalence of DFNB1 mutations in Argentinean children with non-syndromic deafness. 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status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.30672.r82648, Kun Zhang, Department of Genetics, School of Bioscience and Technology, Chengdu Medical College, Chengdu, China, 08 Apr 2021, version 1, 1 approved, 1 approved with reservations","URL":"https:\/\/f1000research.com\/articles\/10-61\/v1#referee-response-82648","order":0,"name":"referee-response-82648","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"Sonia Liao<\/b>; \nPosted: 21 May 2021<\/i>; Thanks a lot. We presented\n <\/b>the suggested reference in the new version, please see the 4\nth<\/sup> paragraph of the discussion section..","URL":"https:\/\/f1000research.com\/articles\/10-61\/v2#referee-comment-6699","order":1,"name":"referee-comment-6699","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.57079.r92750, Yuande Tan, Institute of Personalized Medicine, PENN State University, Hershey College of Medicine, Hershey, PA, USA, 06 Sep 2021, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/10-61\/v2#referee-response-92750","order":2,"name":"referee-response-92750","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was supported by grants from the National Natural Science Foundation of China (grant numbers: 81471430 and 81773159). The funding sponsors had no involvement in the research design, data processing, report writing or publication. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":3,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}