ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000001.10) (NC_000001.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
11845407 Brouillard et al. (2002) identified an intragenic deletion and 13 sequence-level mutations (predicted to result in a loss-of-function) in the GLMN gene in 14 unrelated families with autosomal dominant glomuvenous malformations (GVMs), including an 8.4 kb intragenic deletion removing exons 8-13 and two nonsense mutations. Acquisition of a somatic ?second hit? GLMN mutation was demonstrated for one individual in this cohort, supporting a 2-hit mode of inheritance for GVMs. The authors also report that, amongst the families studied, observed penetrance of the mutations was 88.6% and rose to 92.7% at age 20 years.
15689436 Brouillard et al. (2005) reported 3 novel frameshift mutations and identify 23 additional families with GLMN mutations and GVM.
22092580 Borroni et al. (2011) describe a novel frameshift mutation (p.Leu374LeufsX4 ) segregating with the phenotype in a family with multiple GVMs. The mutation was absent in 190 controls.

Haploinsufficiency phenotype comments:

Alterations at the GLMN locus are associated with autosomal dominant hereditary glomuvenous malformations (GVMs). Penetrance of this phenotype is age-dependent and may be incomplete; expressivity is variable. Somatic 'second hit' mutations are hypothesized to be responsible for the expression of GVMs. Reported mutations are predicted to result in a loss-of-function, however whole gene deletions have not been reported at the time of this literature search.

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