{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:14:31Z","timestamp":1790280871974,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,9,14]],"date-time":"2018-09-14T00:00:00Z","timestamp":1536883200000},"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":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:p>Warsaw breakage syndrome (WBS) is a recently recognized <jats:italic>DDX11<\/jats:italic>\u2010related rare cohesinopathy, characterized by severe prenatal and postnatal growth restriction, microcephaly, developmental delay, cochlear anomalies, and sensorineural hearing loss. Only seven cases have been reported in the English literature, and thus the information on the phenotype and genotype of this interesting condition is limited. We provide clinical and molecular information on five additional unrelated patients carrying novel bi\u2010allelic variants in the <jats:italic>DDX11<\/jats:italic> gene, identified via whole exome sequencing. One of the variants was found to be a novel Saudi founder variant. All identified variants were classified as pathogenic or likely pathogenic except for one that was initially classified as a variant of unknown significance (VOUS) (p.Arg378Pro). Functional characterization of this VOUS using heterologous expression of wild type and mutant DDX11 revealed a marked effect on protein stability, thus confirming pathogenicity of this variant. The phenotypic data of the seven WBS reported patients were compared to our patients for further phenotypic delineation. Although all the reported patients had cochlear hypoplasia, one patient also had posterior labyrinthine anomaly. We conclude that while the cardinal clinical features in WBS (microcephaly, growth retardation, and cochlear anomalies) are almost universally present, the <jats:italic>breakage<\/jats:italic> phenotype is highly variable and can be absent in some cases. This report further expands the knowledge of the phenotypic and molecular features of WBS.<\/jats:p>","DOI":"10.1002\/ajmg.a.40482","type":"journal-article","created":{"date-parts":[[2018,9,16]],"date-time":"2018-09-16T10:20:04Z","timestamp":1537093204000},"page":"2404-2418","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Warsaw breakage syndrome: Further clinical and genetic delineation"],"prefix":"10.1002","volume":"176","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9026-7002","authenticated-orcid":false,"given":"Ebba","family":"Alkhunaizi","sequence":"first","affiliation":[{"name":"The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology Mount Sinai Hospital, University of Toronto  Toronto Ontario Canada"},{"name":"Division of Clinical and Metabolic Genetics, Department of Pediatrics The Hospital for Sick Children, University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranad","family":"Shaheen","sequence":"additional","affiliation":[{"name":"Department of Genetics King Faisal Specialist Hospital and Research Center  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay Kumar","family":"Bharti","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Gerontology National Institute on Aging, National Institutes of Health, NIH Biomedical Research Center  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann M.","family":"Joseph\u2010George","sequence":"additional","affiliation":[{"name":"Cytogenomics Laboratory, Division of Genome Diagnostics, Department of Pediatric Laboratory Medicine The Hospital for Sick Children, University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Chong","sequence":"additional","affiliation":[{"name":"The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology Mount Sinai Hospital, University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2893-8802","authenticated-orcid":false,"given":"Ghada M. 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