ClinGen Dosage Sensitivity Curation Page

CHM

  • Curation Status: Complete

Location Information

Select assembly: (NC_000023.10) (NC_000023.11)
  • Haploinsufficiency score: 3
  • Strength of Evidence (disclaimer): Sufficient evidence for dosage pathogenicity
  • Haploinsufficiency Phenotype: CHOROIDEREMIA; CHM
Evidence for haploinsufficiency phenotype
PubMed ID Description
8477262 Schwartz et al. (1993) tested 12 unrelated patients with choroideremia for mutations in the CHM gene (REP-1). They found mutations in six patients, including a deletion of exon 4, deletion of exons 1-4, a 2 bp deletion, a 4 bp deletion, a nonsense mutation, and a splice site mutation. The splice site mutation was found in the proband's mother, but not in the unaffected brother.
9067750 van den Hurk et al. (1997) provided a mutation update of REP-1 (CHM gene). They reported 7 nonsense mutations in patients with CHM (two of which were from their present study) and 7 frameshift mutations resulting in premature stop codons (one of which was from the present study).
Gene reviews provides additional evidence for this gene.

Haploinsufficiency phenotype comments:

X-linked disorder characterized by progressive retinal degeneration in males and typically asymptomatic or milder phenotype in females.

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.