ClinGen Dosage Sensitivity Curation Page

IQSEC2

  • Curation Status: Complete

Location Information

Select assembly: (NC_000023.10) (NC_000023.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
20473311 The paper by Shoubridge describes missense mutations in males with intellectual disability. "In addition to moderate to severe intellectual disability in all affected males, seizures, autistic traits, psychiatric problems and delayed early language skills were noted, although none of these additional phenotypes were consistent in all affected individuals in the families." The authors showed the mutations reduced the expression of the protein.
21479374 Morleo et al describe a female patient with a t(X;20) with a severe phenotype that included intellectual disability, infantile seizures, and developmental delay. The authors used BAC FISH to map the breakpoints and found the translocation disrupted IQSEC2, between exons 1 and 2 of the longest transcript, which may also disrupt 5' regulatory sequences for the shorter trasncripts.
23674175 The article by Mau-Them et al describes two de novo intragenic duplications and a nonsense mutation in males with severe syndromic ID characterised by "progressive postnatal microcephaly, absence of speech and midline stereotypic hand movements similar to those observed in Rett or variant Rett syndromes." This article also cites the Gandomi reference describing two males with similar features who both have de novo truncating mutations.

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.