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.
Academic Unit of Medical Genetics, St Mary's Hospital, Manchester, UK.
Emma
E
Hilton
Jennifer
J
Johnston
Sandra
S
Whalen
Nobuhiko
N
Okamoto
Yoshikazu
Y
Hatsukawa
Juntaro
J
Nishio
Hiroshi
H
Kohara
Yoshiko
Y
Hirano
Seiji
S
Mizuno
Chiharu
C
Torii
Kenjiro
K
Kosaki
Sylvie
S
Manouvrier
Odile
O
Boute
Rahat
R
Perveen
Caroline
C
Law
Anthony
A
Moore
David
D
Fitzpatrick
Johannes
J
Lemke
Florence
F
Fellmann
François-Guillaume
FG
Debray
Florence
F
Dastot-Le-Moal
Marion
M
Gerard
Josiane
J
Martin
Pierre
P
Bitoun
Michel
M
Goossens
Alain
A
Verloes
Albert
A
Schinzel
Deborah
D
Bartholdi
Tanya
T
Bardakjian
Beverly
B
Hay
Kim
K
Jenny
Kathreen
K
Johnston
Michael
M
Lyons
John W
JW
Belmont
Leslie G
LG
Biesecker
Irina
I
Giurgea
Graeme
G
Black
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