{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:40:58Z","timestamp":1791225658537,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2014,5,19]],"date-time":"2014-05-19T00:00:00Z","timestamp":1400457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2014,9]]},"abstract":"<jats:sec><jats:label\/><jats:p>Mutations in <jats:italic>WDR62<\/jats:italic> are associated with primary microcephaly; however, they have been reported with wide phenotypic variability. We report on six individuals with novel <jats:italic>WDR62<\/jats:italic> mutations who illustrate this variability and describe three in greater detail. Of the three, one lacks neuromotor development and has severe pachygyria on MRI, another has only delayed speech and motor development and moderate polymicrogyria, and the third has an intermediate phenotype. We observed a rare copy number change of unknown significance, a 17q25qter duplication, in the first severely affected individual. The 17q25 duplication included an interesting candidate gene, tubulin cofactor D (<jats:italic>TBCD<\/jats:italic>), crucial in microtubule assembly and disassembly. Sequencing of the non\u2010duplicated allele showed a <jats:italic>TBCD<\/jats:italic> missense mutation, predicted to cause a deleterious p.Phe1121Val substitution. Sequencing of a cohort of five patients with <jats:italic>WDR62<\/jats:italic> mutations, including one with an identical mutation and different phenotype, plus 12 individuals with diagnosis of microlissencephaly and another individual with mild intellectual disability (ID) and a 17q25 duplication, did not reveal <jats:italic>TBCD<\/jats:italic> mutations. However, immunostaining with tubulin antibodies of cells from patients with both <jats:italic>WDR62<\/jats:italic> and <jats:italic>TBCD<\/jats:italic> mutation showed abnormal tubulin network when compared to controls and cells with only the <jats:italic>WDR62<\/jats:italic> mutation. Therefore, we propose that genetic factors contribute to modify the severity of the <jats:italic>WDR62<\/jats:italic> phenotype and, although based on suggestive evidence, TBCD could function as one of such factors. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36611","type":"journal-article","created":{"date-parts":[[2014,5,19]],"date-time":"2014-05-19T20:20:55Z","timestamp":1400530855000},"page":"2161-2171","source":"Crossref","is-referenced-by-count":34,"title":["Severe presentation of <i>WDR62<\/i> mutation: Is there a role for modifying genetic factors?"],"prefix":"10.1002","volume":"164","author":[{"given":"Cathryn J.","family":"Poulton","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics Erasmus Medical Center Rotterdam Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Schot","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Erasmus Medical Center Rotterdam Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Seufert","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics Albert\u2010Ludwigs University Medical Centre Freiburg Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten H.","family":"Lequin","sequence":"additional","affiliation":[{"name":"Department of Radiology Erasmus Medical Center Rotterdam Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Accogli","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Gaslini Institute Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe D'","family":"Annunzio","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Gaslini Institute Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6657-5008","authenticated-orcid":false,"given":"Laurent","family":"Villard","sequence":"additional","affiliation":[{"name":"Inserm U910 Aix Marseille University Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Philip","sequence":"additional","affiliation":[{"name":"Inserm U910 Aix Marseille University Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"de Coo","sequence":"additional","affiliation":[{"name":"Department of Child Neurology Erasmus Medical Center Rotterdam Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coriene","family":"Catsman\u2010Berrevoets","sequence":"additional","affiliation":[{"name":"Department of Child Neurology Erasmus Medical Center Rotterdam Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute","family":"Grasshoff","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Applied Genomics University Hospital Tuebingen Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Kattentidt\u2010Mouravieva","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Erasmus Medical Center Rotterdam Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Calf","sequence":"additional","affiliation":[{"name":"ASVZ Zuid West Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"de Vreugt\u2010Gronloh","sequence":"additional","affiliation":[{"name":"ASVZ Zuid West Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leontine","family":"van Unen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Erasmus Medical Center Rotterdam Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frans W.","family":"Verheijen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Erasmus Medical Center Rotterdam Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"Galjart","sequence":"additional","affiliation":[{"name":"Department of Cell Biology Erasmus Medical Center Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah J.","family":"Morris\u2010Rosendahl","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics Albert\u2010Ludwigs University Medical Centre Freiburg Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grazia M. 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