{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:37:26Z","timestamp":1753871846300,"version":"3.41.2"},"reference-count":40,"publisher":"Portland Press Ltd.","issue":"6","license":[{"start":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T00:00:00Z","timestamp":1608508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,6,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Waardenburg syndrome (WS) is a congenital hereditary disease, attributed to the most common symptoms of sensorineural deafness and iris hypopigmentation. It is also known as the hearing-pigmentation deficient syndrome. Mutations on SOXl0 gene often lead to congenital deafness and has been shown to play an important role in the pathogenesis of WS. We investigated one family of five members, with four patients exhibiting the classic form of WS2, whose DNA samples were analyzed by the technique of Whole-exome sequencing (WES). From analysis of WES data, we found that both the mother and all three children in the family have a heterozygous mutation on the Sex Determining Region Y - Box 10 (SOX10) gene. The mutation was c.298_300delinsGG in exon 2 of SOX10 (NM_006941), which leads to a frameshift of nine nucleotides, hence the amino acids (p. S100Rfs*9) are altered and the protein translation may be terminated prematurely. Further flow cytometry confirmed significant down-regulation of SOX10 protein, which indicated the SOX10 gene mutation was responsible for the pathogenesis of WS2 patients. In addition, we speculated that some other mutated genes might be related to disease phenotype in this family, which might also participate in promoting the progression of WS2.<\/jats:p>","DOI":"10.1042\/bsr20193375","type":"journal-article","created":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T09:42:46Z","timestamp":1608543766000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Waardenburg syndrome type II in a Chinese pedigree caused by frameshift mutation in the <i>SOX10<\/i> gene"],"prefix":"10.1042","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3944-906X","authenticated-orcid":false,"given":"Li","family":"Li","sequence":"first","affiliation":[{"name":"Kunming Key Laboratory of Children Infection and Immunity, Yunnan Key Laboratory of Children\u2019s Major Disease Research, Yunnan Medical Center for Pediatric Diseases, Yunnan Institute of Pediatrics, Kunming Children\u2019s Hospital, Kunming 650228, Yunnan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery, Kunming Children\u2019s Hospital, Kunming 650228, Yunnan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-li","family":"He","sequence":"additional","affiliation":[{"name":"Kunming Key Laboratory of Children Infection and Immunity, Yunnan Key Laboratory of Children\u2019s Major Disease Research, Yunnan Medical Center for Pediatric Diseases, Yunnan Institute of Pediatrics, Kunming Children\u2019s Hospital, Kunming 650228, Yunnan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan-tao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Kunming Key Laboratory of Children Infection and Immunity, Yunnan Key Laboratory of Children\u2019s Major Disease Research, Yunnan Medical Center for Pediatric Diseases, Yunnan Institute of Pediatrics, Kunming Children\u2019s Hospital, Kunming 650228, Yunnan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Kunming Key Laboratory of Children Infection and Immunity, Yunnan Key Laboratory of Children\u2019s Major Disease Research, Yunnan Medical Center for Pediatric Diseases, Yunnan Institute of Pediatrics, Kunming Children\u2019s Hospital, Kunming 650228, Yunnan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Quan-dong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery, Kunming Children\u2019s Hospital, Kunming 650228, Yunnan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiology, Kunming Children\u2019s Hospital, Kunming 650228, Yunnan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Biao","family":"Ruan","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, First Hospital of Kunming Medical University, Kunming 650228, Yunnan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tie-Song","family":"Zhang","sequence":"additional","affiliation":[{"name":"Kunming Key Laboratory of Children Infection and Immunity, Yunnan Key Laboratory of Children\u2019s Major Disease Research, Yunnan Medical Center for Pediatric Diseases, Yunnan Institute of Pediatrics, Kunming Children\u2019s Hospital, Kunming 650228, Yunnan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2021,6,18]]},"reference":[{"key":"2021111620364153400_B1","first-page":"195","article-title":"A new syndrome combining developmental anomalies of the eyelids, eyebrows and nose root with pigmentary defects of the iris and head hair and with congenital deafness","volume":"3","author":"Waardenburg","year":"1951","journal-title":"Am. J. Hum. Genet."},{"key":"2021111620364153400_B2","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1002\/humu.21211","article-title":"Review and update of mutations causing Waardenburg syndrome","volume":"31","author":"Pingauh","year":"2010","journal-title":"Hum. Mutat."},{"key":"2021111620364153400_B3","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1186\/s13256-018-1704-1","article-title":"A rare case of seven siblings with Waardenburg syndrome: a case report","volume":"12","author":"Haj Kassem","year":"2018","journal-title":"J. Med. Case Rep."},{"key":"2021111620364153400_B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1055\/s-0037-1617454","article-title":"Syndromic hearing loss: a brief review of common presentations and genetics","volume":"7","author":"Gettelfinger","year":"2018","journal-title":"J. Pediatr. Genet."},{"key":"2021111620364153400_B5","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1136\/jmg.34.8.656","article-title":"Waardenburg syndrome","volume":"34","author":"Read","year":"1997","journal-title":"J. Med. Genet."},{"key":"2021111620364153400_B6","doi-asserted-by":"publisher","first-page":"1907","DOI":"10.1093\/hmg\/9.13.1907","article-title":"Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg syndrome","volume":"9","author":"Bondurand","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"2021111620364153400_B7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s004390000328","article-title":"Transcription factor hierarchy in Waardenburg syndrome: regulation of MITF expression by SOX10 and PAX3","volume":"107","author":"Potterf","year":"2000","journal-title":"Hum. Genet."},{"key":"2021111620364153400_B8","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1038\/ng0298-171","article-title":"SOX10 mutations in patients with Waardenburg-Hirschsprung disease","volume":"18","author":"Pingault","year":"1998","journal-title":"Nat. Genet."},{"key":"2021111620364153400_B9","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1086\/522090","article-title":"Deletions at the SOX10 gene locus cause Waardenburg syndrome types 2 and 4","volume":"81","author":"Bondurand","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"2021111620364153400_B10","doi-asserted-by":"publisher","first-page":"e30","DOI":"10.1136\/jmg.38.9.e30","article-title":"Novel mutations of SOX10 suggest a dominant negative role in Waardenburg-Shah syndrome","volume":"38","author":"Sham","year":"2001","journal-title":"J. Med. Genet."},{"key":"2021111620364153400_B11","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1093\/hmg\/ddi442","article-title":"Deletion of long-range sequences at Sox10 compromises developmental expression in a mouse model of Waardenburg-Shah (WS4) syndrome","volume":"15","author":"Antonellis","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"2021111620364153400_B12","doi-asserted-by":"publisher","first-page":"1968","DOI":"10.1002\/ajmg.a.40362","article-title":"Biallelic deletions of the Waardenburg II syndrome gene, SOX10, cause a recognizable arthrogryposis syndrome","volume":"176","author":"Stevenson","year":"2018","journal-title":"Am. J. Med. Genet. A"},{"key":"2021111620364153400_B13","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1093\/hmg\/ddg107","article-title":"Sox10 and Pax3 physically interact to mediate activation of a conserved c-RET enhancer","volume":"12","author":"Lang","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"2021111620364153400_B14","doi-asserted-by":"publisher","first-page":"3047","DOI":"10.1093\/nar\/28.16.3047","article-title":"The glial transcription factor Sox10 binds to DNA both as monomer and dimer with different functional consequences","volume":"28","author":"Peirano","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"2021111620364153400_B15","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1101\/gad.186601","article-title":"The transcription factor Sox10 is a key regulator of peripheral glial development","volume":"15","author":"Britsch","year":"2001","journal-title":"Genes Dev."},{"key":"2021111620364153400_B16","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1002\/ana.10404","article-title":"Congenital hypomyelinating neuropathy, central dysmyelination, and Waardenburg-Hirschsprung disease: phenotypes linked by SOX10 mutation","volume":"52","author":"Inoue","year":"2002","journal-title":"Ann. Neurol."},{"key":"2021111620364153400_B17","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1186\/s12887-018-1139-2","article-title":"A case report of reversible generalized seizures in a patient with Waardenburg syndrome associated with a novel nonsense mutation in the penultimate exon of SOX10","volume":"18","author":"Suzuki","year":"2018","journal-title":"BMC Pediatr."},{"key":"2021111620364153400_B18","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1016\/0092-8674(94)90016-7","article-title":"A missense mutation of the endothelin-B receptor gene in multigenic Hirschsprung\u2019s disease","volume":"79","author":"Puffenberger","journal-title":"Cell"},{"key":"2021111620364153400_B19","first-page":"303","article-title":"Endothelin receptor-mediated signaling in hirschsprung disease","volume":"5","author":"Chakravarti","year":"1996","journal-title":"Hum. Mol. Genet."},{"key":"2021111620364153400_B20","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1016\/j.ejmg.2018.01.012","article-title":"Waardenburg syndrome: novel mutations in a large Brazilian sample","volume":"61","author":"Bocangel","year":"2018","journal-title":"Eur. J. Med. Genet."},{"key":"2021111620364153400_B21","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1016\/j.mjafi.2017.05.009","article-title":"Waardenburg syndrome type 2","volume":"74","author":"Shaw","year":"2018","journal-title":"Med. J. Armed Forces India"},{"key":"2021111620364153400_B22","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1002\/bies.201600100","article-title":"Exaptive origins of regulated mRNA decay in eukaryotes","volume":"38","author":"Hamid","year":"2016","journal-title":"Bioessays"},{"key":"2021111620364153400_B23","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1093\/nar\/gkx1272","article-title":"Nonsense-mediated mRNA decay: a \u2018nonsense\u2019 pathway makes sense in stem cell biology","volume":"46","author":"Han","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"2021111620364153400_B24","doi-asserted-by":"publisher","first-page":"a032862","DOI":"10.1101\/cshperspect.a032862","article-title":"Nonsense-mediated mRNA decay begins where translation ends","volume":"11","author":"Karousis","year":"2019","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"2021111620364153400_B25","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.ijporl.2016.03.043","article-title":"Waardenburg syndrome type II in a Chinese patient caused by a novel nonsense mutation in the SOX10 gene","volume":"85","author":"Ma","year":"2016","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"2021111620364153400_B26","first-page":"1512831","article-title":"A novel nonsense mutation of POU4F3 gene causes autosomal dominant hearing loss","volume":"8","author":"Zhang","year":"2016","journal-title":"Neural Plast."},{"key":"2021111620364153400_B27","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1038\/jhg.2016.102","article-title":"Exome sequencing identifies POU4F3 as the causative gene for a large Chinese family with non-syndromic hearing loss","volume":"62","author":"Cai","year":"2017","journal-title":"J. Hum. Genet."},{"key":"2021111620364153400_B28","doi-asserted-by":"publisher","first-page":"e691","DOI":"10.1097\/MAO.0000000000001896","article-title":"Audiologic manifestations of Marshall syndrome","volume":"39","author":"Bacciu","year":"2018","journal-title":"Otol. Neurotol."},{"key":"2021111620364153400_B29","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1007\/s12041-017-0874-8","article-title":"A genetic variant in COL11A1 is functionally associated with lumbar disc herniation in Chinese population","volume":"96","author":"Liu","year":"2017","journal-title":"J. Genet."},{"key":"2021111620364153400_B30","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1111\/bjd.16323","article-title":"Iris pigmented lesions as a marker of cutaneous melanoma risk: an Australian case-control study","volume":"178","author":"Laino","year":"2018","journal-title":"Br. J. Dermatol."},{"key":"2021111620364153400_B31","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1002\/mgg3.213","article-title":"Importance of nonsynonymous OCA2 variants in human eye color prediction","volume":"4","author":"Andersen","year":"2016","journal-title":"Mol. Genet. Genom. Med."},{"key":"2021111620364153400_B32","doi-asserted-by":"publisher","first-page":"1983","DOI":"10.3892\/mmr.2016.4774","article-title":"Clinical and genetic investigation of families with type II Waardenburg syndrome","volume":"13","author":"Chen","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"2021111620364153400_B33","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1002\/humu.21211","article-title":"Review and update of mutations causing Waardenburg Syndrome","volume":"31","author":"Pingault","year":"2010","journal-title":"Hum. Mutat."},{"key":"2021111620364153400_B34","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1089\/cell.2014.0032","article-title":"Hepatocyte-ductal transdifferentiation is mediated by reciprocal repression of SOX9 and C\/EBPalpha","volume":"16","author":"O\u2019Neill","year":"2014","journal-title":"Cell. Reprogram."},{"key":"2021111620364153400_B35","doi-asserted-by":"publisher","first-page":"1439","DOI":"10.1093\/hmg\/ddg158","article-title":"Loss of DNA-dependent dimerization of the transcription factor SOX9 as a cause for campomelic dysplasia","volume":"12","author":"Sock","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"2021111620364153400_B36","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1111\/j.1600-0749.2007.00368.x","article-title":"The tyrosinase enhancer is activated by Sox10 and Mitf in mouse melanocytes","volume":"20","author":"Murisier","year":"2007","journal-title":"Pigment Cell Res."},{"key":"2021111620364153400_B37","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.semcdb.2013.03.014","article-title":"Pleiotropic effects of coat colour-associated mutations in humans, mice and other mammals","volume":"24","author":"Reissmann","year":"2013","journal-title":"Semin. Cell Dev. Biol."},{"key":"2021111620364153400_B38","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1034\/j.1600-0749.13.s8.23.x","article-title":"Molecular bases of congenital hypopigmentary disorders in humans and oculocutaneous albinism 1 in Japan","volume":"13","author":"Tomita","year":"2000","journal-title":"Pigment Cell Res."},{"key":"2021111620364153400_B39","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1016\/S1097-2765(00)80384-6","article-title":"A C\/EBP beta isoform recruits the SWI\/SNF complex to activate myeloid genes","volume":"4","author":"Kowenz-Leutz","year":"1999","journal-title":"Mol. Cell."},{"key":"2021111620364153400_B40","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1016\/j.bbrc.2016.06.105","article-title":"Vasoactive intestinal peptide stimulates melanogenesis in B16F10 mouse melanoma cells via CREB\/MITF\/tyrosinase signaling","volume":"477","author":"Yuan","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."}],"container-title":["Bioscience Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/doi\/10.1042\/BSR20193375\/915193\/bsr-2019-3375.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/doi\/10.1042\/BSR20193375\/915193\/bsr-2019-3375.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T21:01:24Z","timestamp":1637096484000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/bioscirep\/article\/41\/6\/BSR20193375\/227397\/Waardenburg-syndrome-type-II-in-a-Chinese-pedigree"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6]]},"references-count":40,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6,25]]}},"URL":"https:\/\/doi.org\/10.1042\/bsr20193375","relation":{},"ISSN":["0144-8463","1573-4935"],"issn-type":[{"type":"print","value":"0144-8463"},{"type":"electronic","value":"1573-4935"}],"subject":[],"published-other":{"date-parts":[[2021,6]]},"published":{"date-parts":[[2021,6]]},"article-number":"BSR20193375"}}