BCOR analysis in patients with OFCD and Lenz microphthalmia syndromes, mental retardation with ocular anomalies, and cardiac laterality defects


Emma Hilton, University of Manchester
Jennifer Johnston, National Human Genome Research Institute
Sandra Whalen, Institut Mondor de Recherche Biomédicale
Nobuhiko Okamoto, Osaka Medical Centre and Research Institute
Yoshikazu Hatsukawa, Osaka Medical Centre and Research Institute
Juntaro Nishio, Osaka Medical Centre and Research Institute
Hiroshi Kohara, Osaka Medical Centre and Research Institute
Yoshiko Hirano, Osaka Medical Centre and Research Institute
Seiji Mizuno, Aichi Human Service Centre
Chiharu Torii, Keio University School of Medicine
Kenjiro Kosaki, Keio University School of Medicine
Sylvie Manouvrier, Centre Hospitalier Regional Universitaire de Lille
Odile Boute, Centre Hospitalier Regional Universitaire de Lill
Rahat Perveen, St. Mary's Hospital
Caroline Law, Princess Anne Hospital
Anthony Moore, Moorfields Eye Hospital
David Fitzpatrick, Western General Hospital
Johannes Lemke, Universitat Zurich
Florence Fellmann, Centre Hospitalier Universitaire Vaudois
Francois-Guillaume Debray, Centre Hospitalier Universitaire Sart Tilman
Florence Dastot-Le-Moal, Universite Paris XII
Marion Gerard, Hopital Robert Debre
Josiane Martin, Institut Mondor de Recherche Biomedicale
Pierre Bitoun, Hôpital Jean Verdier
Michel Goossens, Institut Mondor de Recherche Biomedicale
Alain Verloes, Hopital Robert Debre
Albert Schinzel, Universitat Zurich
Deborah Bartholdi, Universitat Zurich
Tanya Bardakjian, Albert Einstein Medical Centre
Beverly N. Hay, University of Massachusetts Medical SchoolFollow
Kim Jenny, AI DuPont Hospital for Children
Kathreen Johnston, The Permanente Medical Group Inc
Michael Lyons, Stanford University School of Medicine
John W. Belmont, Baylor College of Medicine
Leslie G. Biesecker, National Human Genome Research Institute
Irina Giurgea, Institut Mondor de Recherche Biomedicale,
Graeme Black, St. Mary's Hospital

UMMS Affiliation

Department of Pediatrics

Publication Date


Document Type



Adolescent; Adult; Aged; Alleles; Animals; Child; Child, Preschool; Cohort Studies; Eye Abnormalities; Female; Genetic Diseases, X-Linked; Heart Diseases; Humans; Infant, Newborn; Male; Mental Retardation; Microphthalmos; Middle Aged; Proto-Oncogene Proteins; Repressor Proteins; Syndrome


Genetics and Genomics | Medical Genetics | Pediatrics


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.

DOI of Published Version



Eur J Hum Genet. 2009 Oct;17(10):1325-35. Epub 2009 Apr 15. Link to article on publisher's site

Journal/Book/Conference Title

European journal of human genetics : EJHG

Related Resources

Link to Article in PubMed

PubMed ID