ClinGen Dosage Sensitivity Curation Page

BCOR

  • Curation Status: Complete

Location Information

Select assembly: (NC_000023.10) (NC_000023.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
19367324 Hilton et al. (2009) performed BCOR mutation analysis in patients with oculofacialcardiodental syndrome (OFCD), Lenz microphthalmia syndrome, isolated ocular anomalies, and isolated cardiac laterality defects and provide a review of the literature. Amongst those with OFCD, several novel nonsense, frameshift, and intragenic deletions were detected. Only a single missense mutation was identified in an individual with Lenz microphthalmia, and no mutations were identified amongst those with isolated cardiac laterality defects.
15770227 Horn et al. (2005) report two frameshift mutations and one deletion amongst three unrelated female patients with oculofacialcardiodental syndrome (OFCD). The deletion was found to be de novo and thought to be at least 60kb in size, removing at least exons 2-15 of the BCOR gene.

Haploinsufficiency phenotype comments:

Mutations in the BCOR gene have been described in two allelic X-linked microphthalmia syndromes: In females, heterozygous whole- and partial-gene deletions, as well as sequence-level BCOR mutations that result in a loss-of-function cause Oculo-facio-cardio-dental (OFCD) syndrome, an X-linked dominant condition with male lethality. In males, a missense BCOR mutation 254C>T (p.Pro85Leu) has been described in association with Lenz microphthalmia syndrome, a heterogeneous X-linked recessive condition.

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.