ClinGen Dosage Sensitivity Curation Page

PRPS1

  • Curation Status: Complete

Location Information

Select assembly: (NC_000023.10) (NC_000023.11)

Haploinsufficiency phenotype comments:

Missense mutations that lead to loss of PRPS1 enzyme activity have been associated with a spectrum of PRPS1-related disorders including Arts syndrome (OMIM: 301835; http://www.ncbi.nlm.nih.gov/books/NBK2591/), Charcot-Marie-Tooth Neuropathy X type 5 (OMIM: 311070; http://www.ncbi.nlm.nih.gov/books/NBK1876/), and non-syndromic X-linked sensorineural deafness (OMIM: 304500; http://www.ncbi.nlm.nih.gov/books/NBK57098/). Gain of function mutations in PRPS1 result in PRPS Superactivity (OMIM: 300661; http://www.ncbi.nlm.nih.gov/books/NBK1973). All of these conditions are rare but more than three independent probands with missense mutations resulting in loss of enzyme function have been reported within the group of disorders. See individual GeneReviews for complete clinical information as well as a review by de Brouwer et al (PMID:20380929).

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.