ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000011.9) (NC_000011.10)
Evidence for haploinsufficiency phenotype
PubMed ID Description
12172548 This paper describes a1479_1484delGTGGAT change found in a 6 generation family with 29 affected individuals. This change was not found in 153 normal chromosomes. Another family is also described in this paper with a smaller intragenic deletion.
15223780 This paper describes several families/mutations, including Q505X in a 3 generation family (3 affected in two generations).
14507768 This paper also describes several families/mutations, including W319X in an apparent simplex family.

Haploinsufficiency phenotype comments:

Per GeneReviews, only 4-20% of the phenotype is attributed to this gene. Phenotype also attributed to mutations in another gene, LRP5. There are believed to be other loci involved as well. Phenotype is quite variable in age of onset and severity, but there have been reports of severely affected infants. Regarding penetrance: "When using fluorescein angiography to determine clinical status, penetrance is reported to be 100% because all affected individuals have a sector of avascular peripheral retina [Ober et al 1980]. When using examination of the retina with an indirect ophthalmoscope through a dilated pupil to determine clinical status, penetrance is considered to be about 90% [van Nouhuys 1982]. When using reduced vision or other clinical symptoms to determine clinical status, penetrance as low as 10% is reported." (GeneReviews) Changes within this gene are also thought to possibly be related to retinopathy of prematurity (PMID: 20141357, 20008721).

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

Triplosensitivity phenotype comment:

A triplosensitive phenotype has yet to be reported for this gene.