ClinGen Dosage Sensitivity Curation Page

FGD1

  • Curation Status: Complete

Location Information

Select assembly: (NC_000023.10) (NC_000023.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
17152066 In 2 brothers with Aarskog-Scott syndrome (AAS), Orrico et al. (2006) identified a novel truncating mutation in the FGD1 gene, consisting of a 1 basepair insertion in exon 4 (945insC). This insertion leads to a frameshift with premature termination at codon 319. The resulting protein either lacks all functionally important structural elements or undergoes nonsense-mediated decay, leading to complete absence of a functional protein.
20082460 Orrico et al. (2010) screened 60 European patients with a clinically suspected diagnosis of AAS for mutations in the FGD1 gene. They identified nine novel mutations in 11 patients, including four truncating mutations (p.Y530X; p.R656X; c.806delC; c.1620delC) and the first reported splice site mutation (c.1935?3A>C). See Table 1 for a summary of the mutations.

Haploinsufficiency phenotype comments:

Mutations in FDG1 cause Aarskog-Scott syndrome (AAS), also known as facio-digito-genital dysplasia.

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.