ClinGen Dosage Sensitivity Curation Page

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DKC1

  • Curation Status: Complete

Location Information

Select assembly: (NC_000023.10) (NC_000023.11)
  • Haploinsufficiency score: 1
  • Strength of Evidence (disclaimer): Little evidence for dosage pathogenicity
Evidence for haploinsufficiency phenotype
PubMed ID Description
18627054 Pearson (2008): A report of a male patient with Hoyeraal-Hreidarsson syndrome (a severe form of dyskeratosis congenita) who had a mutation identified at IVS12+1 which resulted in a retention of intron 12 and a premature truncation. The mutation was found in the patient's unaffected carrier mother.

Haploinsufficiency phenotype comments:

Many mutations in DKC1 have been described in patients with X-linked dyskeratosis congenita and Hoyeraal-Hreidarsson syndrome. However, the vast majority of these are missense mutations. The exceptions to this include the patient described above by Pearson et al. as well as one patient with a 2 kb deletion that partially overlaps the 3' end of DKC1 (normal transcription was observed), PMID: 9590285 and 10438713. There have not been any mutations described that clearly indicate that loss of function is a mechanism of disease.

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.