| BCOR analysis in patients with OFCD and Lenz microphthalmia syndromes, mental retardation with ocular anomalies, and cardiac laterality defects. | |
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MedLine Citation:
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PMID: 19367324 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Oculofaciocardiodental (OFCD) and Lenz microphthalmia syndromes form part of a spectrum of X-linked microphthalmia disorders characterized by ocular, dental, cardiac and skeletal anomalies and mental retardation. The two syndromes are allelic, caused by mutations in the BCL-6 corepressor gene (BCOR). To extend the series of phenotypes associated with pathogenic mutations in BCOR, we sequenced the BCOR gene in patients with (1) OFCD syndrome, (2) putative X-linked ('Lenz') microphthalmia syndrome, (3) isolated ocular defects and (4) laterality phenotypes. We present a new cohort of females with OFCD syndrome and null mutations in BCOR, supporting the hypothesis that BCOR is the sole molecular cause of this syndrome. We identify for the first time mosaic BCOR mutations in two females with OFCD syndrome and one apparently asymptomatic female. We present a female diagnosed with isolated ocular defects and identify minor features of OFCD syndrome, suggesting that OFCD syndrome may be mild and underdiagnosed. We have sequenced a cohort of males diagnosed with putative X-linked microphthalmia and found a mutation, p.P85L, in a single case, suggesting that BCOR mutations are not a major cause of X-linked microphthalmia in males. The absence of BCOR mutations in a panel of patients with non-specific laterality defects suggests that mutations in BCOR are not a major cause of isolated heart and laterality defects. Phenotypic analysis of OFCD and Lenz microphthalmia syndromes shows that in addition to the standard diagnostic criteria of congenital cataract, microphthalmia and radiculomegaly, patients should be examined for skeletal defects, particularly radioulnar synostosis, and cardiac/laterality defects. |
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Authors:
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Emma Hilton; Jennifer Johnston; Sandra Whalen; Nobuhiko Okamoto; Yoshikazu Hatsukawa; Juntaro Nishio; Hiroshi Kohara; Yoshiko Hirano; Seiji Mizuno; Chiharu Torii; Kenjiro Kosaki; Sylvie Manouvrier; Odile Boute; Rahat Perveen; Caroline Law; Anthony Moore; David Fitzpatrick; Johannes Lemke; Florence Fellmann; François-Guillaume Debray; Florence Dastot-Le-Moal; Marion Gerard; Josiane Martin; Pierre Bitoun; Michel Goossens; Alain Verloes; Albert Schinzel; Deborah Bartholdi; Tanya Bardakjian; Beverly Hay; Kim Jenny; Kathreen Johnston; Michael Lyons; John W Belmont; Leslie G Biesecker; Irina Giurgea; Graeme Black |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't Date: 2009-04-15 |
Journal Detail:
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Title: European journal of human genetics : EJHG Volume: 17 ISSN: 1476-5438 ISO Abbreviation: Eur. J. Hum. Genet. Publication Date: 2009 Oct |
Date Detail:
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Created Date: 2009-09-24 Completed Date: 2009-12-14 Revised Date: 2010-12-03 |
Medline Journal Info:
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Nlm Unique ID: 9302235 Medline TA: Eur J Hum Genet Country: England |
Other Details:
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Languages: eng Pagination: 1325-35 Citation Subset: IM |
Affiliation:
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Academic Unit of Medical Genetics, St Mary's Hospital, Manchester, UK. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Aged Alleles Animals Child Child, Preschool Cohort Studies Eye Abnormalities / complications, genetics* Female Genetic Diseases, X-Linked / complications, genetics Heart Diseases / complications, genetics* Humans Infant, Newborn Male Mental Retardation / complications, genetics* Microphthalmos / complications, genetics* Middle Aged Proto-Oncogene Proteins / genetics* Repressor Proteins / genetics* Syndrome |
| Grant Support | |
ID/Acronym/Agency:
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Z01 HG200328-04/HG/NHGRI NIH HHS; //Wellcome Trust |
| Chemical | |
Reg. No./Substance:
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0/BCOR protein, human; 0/Proto-Oncogene Proteins; 0/Repressor Proteins |
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