ClinGen Dosage Sensitivity Curation Page

FAM58A

  • Curation Status: Complete

Location Information

Select assembly: (NC_000023.10) (NC_000023.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
18297069 Unger et al. (2008) describe FAM58A mutations in girls with a consistent constellation of facial dysmorphism, toe syndactyly, telecanthus and anogenital and renal malformations (STAR syndrome). One individual was found to have a de novo 40,068 bp deletion removing the coding regions of exons 1 and 2 as well as intron 1 (2,774 bp), 492 bp of intron 2, and 36,608 bp of 5' sequence, including the 5' UTR and the entire KRT18P48 pseudogene. Another was found to have a 4,249 bp deletion which removed 1,265 bp of intron 4, all of exon 5, including the 3' UTR, and 2,454 bp of 3' sequence. The remaining individuals were found to have point mutations, including a de novo frameshift mutation 201dupT, which results in a premature stop codon N68XfsX1, and a 555+1G>A splice donor site mutation, and a 556-1G>A splice acceptor site mutation (inherited from an affected mother). None of the mutations were seen in the DNA of 60 unaffected female controls, and no larger deletions involving FAM58A were found in 93 unrelated array-CGH investigations.

Haploinsufficiency phenotype comments:

All individuals reported with deletions or mutations in FAM58A have been female. It is not known what the effect of a loss of function mutation in a male would be.

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.