{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T23:41:56Z","timestamp":1776296516382,"version":"3.50.1"},"reference-count":26,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T00:00:00Z","timestamp":1660608000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Premature ovarian insufficiency (POI) is a clinical syndrome occurring in women before 40 with decreased ovarian function. Up to 25% of POI cases result from genetic factors that remain largely unknown. The Excision repair cross\u2010complementing, group 6 (<jats:italic>ERCC6<\/jats:italic>) variant has been found to cause POI, which is hardly ever diagnosed in adolescents.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole\u2010exome sequencing was performed on a 19\u2010year\u2010old proband with non\u2010syndromic POI and her parents. Sanger sequencing was used to confirm the identified variant. The effect of the variant on the protein was analyzed in silico and Swiss\u2010MODEL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A novel heterozygous missense variant, c.2444G\u2009&gt;\u2009A (p. GLy815Asp) of <jats:italic>ERCC6<\/jats:italic> was identified in the proband who inherited the variant from her father. The variant was confirmed in another POI patient from the pedigree and was absent in the proband's mother and sister who presented normally. In silico analysis predicted this variant was deleterious. Swiss\u2010Model revealed that the mutant amino acid formed multiple H\u2010bonds with adjacent residues, which may lead to a dysfunction of ERCC6 protein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We firstly diagnosed an adolescent POI case associated with a novel heterozygous <jats:italic>ERCC6<\/jats:italic> variant. The results expanded the variants spectrum of <jats:italic>ERCC6<\/jats:italic> and provided guidance for POI diagnosis and genetic counselling.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2040","type":"journal-article","created":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T06:39:40Z","timestamp":1660718380000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A novel heterozygous <i>ERCC6<\/i> variant identified in a Chinese family with non\u2010syndromic primary ovarian insufficiency"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6238-0940","authenticated-orcid":false,"given":"Lele","family":"Kuang","sequence":"first","affiliation":[{"name":"Department of Assisted Reproduction, Xinhua Hospital, School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Assisted Reproduction, Xinhua Hospital, School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Di","family":"Xi","sequence":"additional","affiliation":[{"name":"Department of Assisted Reproduction, Xinhua Hospital, School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuping","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Assisted Reproduction, Xinhua Hospital, School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,8,16]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013786"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/370195"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010017\u201002114\u2010x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016\u20102152"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102017\u2010104877"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005\u20102650"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2021.101594"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0404587101"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399\u20100004.2010.01424.x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.maturitas.2020.06.004"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.maturitas.2019.10.011"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12920\u2010020\u201000813\u2010x"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2019\u201000248"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3109\/09513590.2013.788625"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2013.02.006"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13048\u2010020\u201000645\u20104"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20610"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000031"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005419"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmv036"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10815\u2010021\u201002083\u20107"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.683235"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1820"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dew027"}],"container-title":["Molecular Genetics &amp; 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