ClinGen Dosage Sensitivity Curation Page

ARSE

  • Curation Status: Complete

Location Information

Select assembly: (NC_000023.10) (NC_000023.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
12567415 Brunetti-Pierri et al. (2003) screened 16 male patients with X-linked chondrodysplasia punctata (CDPX1) for mutations in the ARSE gene. Mutations in ARSE were identified in 12 of the 16 patients with nonsense mutations, missense mutations, insertions and whole gene deletions detected. Functional studies of the missense mutations demonstrated decreased catalytic activity of arylsulfatase E
18348268 Nino et al. (2008) evaluated the ARSE gene in 11 patients meeting the clinical criteria for CDPX1 and identified mutations in 7 of them. The mutations reported were 4 missense mutations, a 1-bp duplication resulting in a frameshift and premature termination codon, and two gene deletions.

Haploinsufficiency phenotype comments:

X-linked chondrodysplasia punctata 1 (CPDX1) is a rare disorder of bone and cartilage development characterized by chondrodysplasia punctata, brachytelephalangy, and nasomaxillary hypoplasia. Most affected males have a normal intellect and life span, however some affected individuals have respiratory compromise, cervical spine stenosis, hearing loss, and intellectual disabilities. Affected carrier females have not been described.

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.