BCOR analysis in patients with OFCD and Lenz microphthalmia syndromes, mental retardation with ocular anomalies, and cardiac laterality defects.
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.
Hilton
Emma
E
Academic Unit of Medical Genetics, St Mary's Hospital, Manchester, UK.
Johnston
Jennifer
J
Whalen
Sandra
S
Okamoto
Nobuhiko
N
Hatsukawa
Yoshikazu
Y
Nishio
Juntaro
J
Kohara
Hiroshi
H
Hirano
Yoshiko
Y
Mizuno
Seiji
S
Torii
Chiharu
C
Kosaki
Kenjiro
K
Manouvrier
Sylvie
S
Boute
Odile
O
Perveen
Rahat
R
Law
Caroline
C
Moore
Anthony
A
Fitzpatrick
David
D
Lemke
Johannes
J
Fellmann
Florence
F
Debray
François-Guillaume
FG
Dastot-Le-Moal
Florence
F
Gerard
Marion
M
Martin
Josiane
J
Bitoun
Pierre
P
Goossens
Michel
M
Verloes
Alain
A
Schinzel
Albert
A
Bartholdi
Deborah
D
Bardakjian
Tanya
T
Hay
Beverly
B
Jenny
Kim
K
Johnston
Kathreen
K
Lyons
Michael
M
Belmont
John W
JW
Biesecker
Leslie G
LG
Giurgea
Irina
I
Black
Graeme
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000818:Animals; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005124:Eye Abnormalities / Q000150:complications / Q000235:genetics*; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000150:complications / Q000235:genetics; D006331:Heart Diseases / Q000150:complications / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000150:complications / Q000235:genetics*; D008297:Male; D008850:Microphthalmos / Q000150:complications / Q000235:genetics*; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D013577:Syndrome
C411984:BCOR protein, human; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins