Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Oculofaciocardiodental and Lenz microphthalmia syndromes result from distinct classes of mutations in BCOR. 1500 58

Oculo-facio-cardio-dental (OFCD) syndrome is a rare X-linked dominant condition with male lethality characterized by microphthalmia, congenital cataracts, facial dysmorphic features, congenital heart defects, and dental anomalies. Mutations in BCOR (BCL6 co-repressor) located in Xp11.4 have been described to cause OFCD syndrome. Lenz microphthalmia syndrome is inherited in an X-linked recessive pattern comprising microphthalmia/anophthalmia, mental retardation, malformed ears, digital, skeletal, and urogenital anomalies (synonym: microphthalmia with associated anomalies (MAA)). One locus for MAA has been mapped to Xq27-q28. Nonetheless, linkage and subsequent mutation analysis revealed a single missense mutation (p.P85L) in BCOR in a large family with presumed Lenz microphthalmia syndrome (MAA2). We describe novel mutations in BCOR in three patients with OFCD syndrome, two small deletions (c.2488_2489delAG and c.3286delG) and a submicroscopic deletion of about 60 kb encompassing at least BCOR exons 2-15. No BCOR mutation was detected in eight patients with Lenz microphthalmia syndrome. Our data confirm that BCOR is the causative gene for OFCD syndrome; however, the failure to identify any mutation in patients with Lenz microphthalmia syndrome together with the oligosymptomatic phenotype in the reported MAA2 patients suggest that BCOR is not the major gene for this syndrome.
 ...
PMID:Novel mutations in BCOR in three patients with oculo-facio-cardio-dental syndrome, but none in Lenz microphthalmia syndrome. 1577 Feb 27

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.
 ...
PMID:BCOR analysis in patients with OFCD and Lenz microphthalmia syndromes, mental retardation with ocular anomalies, and cardiac laterality defects. 1936 24