ClinGen Dosage Sensitivity Curation Page

RS1

  • Curation Status: Complete

Location Information

Select assembly: (NC_000023.10) (NC_000023.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
9326935 Sauer et al. (1998) identify RS1 (aka XLRS1) as the gene responsible for retinoschisis. Mutational analyses in nine unrelated families identify one nonsense, one frameshift, one splice acceptor, and six missense mutations in RS1; all of which segregate with disease.
9618178 The Retinoschisis Consortium (1998) screened 234 familial and sporadic retinoschisis cases and identified 82 different mutations in 214 (91%) cases. The mutational spectrum was missense (75%), small intragenic deletions (7%), nonsense (6%), framseshift (6%) and splice site (6%).

Haploinsufficiency phenotype comments:

Affected males show schisis (splitting) of the neural retina leading to reduced visual acuity. Carrier females may also express the disease and display similar clinical findings. The onset of clinical symptoms usually occurs within the first decade, as early as 3 months in some cases.

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 available

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.