{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:35:31Z","timestamp":1789544131499,"version":"build-2803163510"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,9,23]],"date-time":"2020-09-23T00:00:00Z","timestamp":1600819200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Oculo\u2010auriculo\u2010vertebral spectrum (OAVS) [MIM:164210], or Goldenhar syndrome, is a developmental disorder associating defects of structures derived from the first and second branchial arches. The genetic origin of OAVS is supported by the description of rare deleterious variants in a few causative genes, and several chromosomal copy number variations. We describe here a large family with eight male members affected by a mild form of the spectrum, mostly auricular defects, harboring a hemizygous\n                    <jats:italic>ZIC3<\/jats:italic>\n                    variant detected by familial exome sequencing: c.159_161dup p.(Ala55dup), resulting in an expansion of the normal 10 consecutive alanine residues to 11 alanines. Segregation analysis shows its presence in all the affected individuals, with a recessive X\u2010linked transmission. Whole\u2010genome sequencing performed in another affected male allowed to exclude linkage disequilibrium between this\n                    <jats:italic>ZIC3<\/jats:italic>\n                    variant and another potential pathogenic variant in this family. Furthermore, by screening of a cohort of 274 OAVS patients, we found 1 male patient carrying an expansion of 10 to 12 alanines, a variant previously reported in patient presenting with VACTERL. Loss\u2010of\u2010function variants of\n                    <jats:italic>ZIC3<\/jats:italic>\n                    are causing heterotaxy or cardiac malformations. These alanine expansion variants could have a different impact on the protein and thereby resulting in a different phenotype within the OAVS\/VACTERL.\n                  <\/jats:p>","DOI":"10.1111\/cge.13811","type":"journal-article","created":{"date-parts":[[2020,7,8]],"date-time":"2020-07-08T05:45:17Z","timestamp":1594187117000},"page":"384-389","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Description of a family with X\u2010linked oculo\u2010auriculo\u2010vertebral spectrum associated with polyalanine tract expansion in\n                    <scp>\n                      <i>ZIC3<\/i>\n                    <\/scp>"],"prefix":"10.1111","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3457-5684","authenticated-orcid":false,"given":"Aur\u00e9lien","family":"Trimouille","sequence":"first","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale CHU Bordeaux  Bordeaux France"},{"name":"Maladies Rares: G\u00e9n\u00e9tique et M\u00e9tabolisme (MRGM) INSERM U1211, Univ. Bordeaux  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1103-2158","authenticated-orcid":false,"given":"Ang\u00e8le","family":"Tingaud\u2010Sequeira","sequence":"additional","affiliation":[{"name":"Maladies Rares: G\u00e9n\u00e9tique et M\u00e9tabolisme (MRGM) INSERM U1211, Univ. Bordeaux  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didier","family":"Lacombe","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale CHU Bordeaux  Bordeaux France"},{"name":"Maladies Rares: G\u00e9n\u00e9tique et M\u00e9tabolisme (MRGM) INSERM U1211, Univ. Bordeaux  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5201-2124","authenticated-orcid":false,"given":"Tina","family":"Duelund Hjortsh\u00f8j","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University Hospital of Copenhagen  Rigshospitalet Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Kreiborg","sequence":"additional","affiliation":[{"name":"Section of Pediatric Dentistry and Clinical Genetics, Department of Odontology University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanne","family":"Buciek Hove","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University Hospital of Copenhagen  Rigshospitalet Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9789-3591","authenticated-orcid":false,"given":"Caroline","family":"Rooryck","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale CHU Bordeaux  Bordeaux France"},{"name":"Maladies Rares: G\u00e9n\u00e9tique et M\u00e9tabolisme (MRGM) INSERM U1211, Univ. 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