RGD Reference Report - Oculofaciocardiodental and Lenz microphthalmia syndromes result from distinct classes of mutations in BCOR. - Rat Genome Database

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Oculofaciocardiodental and Lenz microphthalmia syndromes result from distinct classes of mutations in BCOR.

Authors: Ng, D  Thakker, N  Corcoran, CM  Donnai, D  Perveen, R  Schneider, A  Hadley, DW  Tifft, C  Zhang, L  Wilkie, AO  Van der Smagt, JJ  Gorlin, RJ  Burgess, SM  Bardwell, VJ  Black, GC  Biesecker, LG 
Citation: Ng D, etal., Nat Genet. 2004 Apr;36(4):411-6. Epub 2004 Mar 7.
RGD ID: 1600504
Pubmed: PMID:15004558   (View Abstract at PubMed)
DOI: DOI:10.1038/ng1321   (Journal Full-text)

Lenz microphthalmia is inherited in an X-linked recessive pattern and comprises microphthalmia, mental retardation, and skeletal and other anomalies. Two loci associated with this syndrome, MAA (microphthalmia with associated anomalies) and MAA2, are situated respectively at Xq27-q28 (refs. 1,2) and Xp11.4-p21.2 (ref. 3). We identified a substitution, nt 254C-->T; P85L, in BCOR (encoding BCL-6-interacting corepressor, BCOR) in affected males from the family with Lenz syndrome previously used to identify the MAA2 locus. Oculofaciocardiodental syndrome (OFCD; OMIM 300166) is inherited in an X-linked dominant pattern with presumed male lethality and comprises microphthalmia, congenital cataracts, radiculomegaly, and cardiac and digital abnormalities. Given their phenotypic overlap, we proposed that OFCD and MAA2-associated Lenz microphthalmia were allelic, and we found different frameshift, deletion and nonsense mutations in BCOR in seven families affected with OFCD. Like wild-type BCOR, BCOR P85L and an OFCD-mutant form of BCOR can interact with BCL-6 and efficiently repress transcription. This indicates that these syndromes are likely to result from defects in alternative functions of BCOR, such as interactions with transcriptional partners other than BCL-6. We cloned the zebrafish (Danio rerio) ortholog of BCOR and found that knock-down of this ortholog caused developmental perturbations of the eye, skeleton and central nervous system consistent with the human syndromes, confirming that BCOR is a key transcriptional regulator during early embryogenesis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cataract  IAGP 1600504DNA:mutations:cds:RGD 
cataract  ISOBCOR (Homo sapiens)1600504; 1600504DNA:mutations:cds:RGD 
syndromic microphthalmia 1  IAGP 1600504DNA:missense mutation:exon:254C>T (p.P85L) (human)RGD 
syndromic microphthalmia 1  ISOBCOR (Homo sapiens)1600504; 1600504DNA:missense mutation:exon:254C>T (p.P85L) (human)RGD 
syndromic microphthalmia 2  IAGP 1600504DNA:mutations:cds:RGD 
syndromic microphthalmia 2  ISOBCOR (Homo sapiens)1600504; 1600504DNA:mutations:cds:RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Microphthalmia  IAGP 1600504DNA:missense mutation:exon:254C>T (p.P85L)RGD 
Persistence of primary teeth  IAGP 1600504DNA:mutations:cds:RGD 
Radiculomegaly  IAGP 1600504DNA:mutations:cds:RGD 
Objects Annotated

Genes (Rattus norvegicus)
Bcor  (BCL6 co-repressor)

Genes (Mus musculus)
Bcor  (BCL6 interacting corepressor)

Genes (Homo sapiens)
BCOR  (BCL6 corepressor)


Additional Information