Four common glomulin mutations cause two thirds of glomuvenous malformations ("familial glomangiomas"): evidence for
P Brouillard1, M Ghassibé, A Penington
1Laboratory of Human Molecular Genetics, Christian de Duve Institute of Cellular Pathology and Université catholique de Louvain, Brussels, Belgium.
Background:
Glomuvenous malformation (GVM) ("familial glomangioma") is a localised cutaneous vascular lesion histologically characterised by abnormal smooth muscle-like "glomus cells" in the walls of distended endothelium lined channels. Inheritable GVM has been linked to chromosome 1p21-22 and is caused by truncating mutations in glomulin. A double hit mutation was identified in one lesion. This finding suggests that GVM results from complete localised loss of function and explains the paradominant mode of inheritance.
Objective:
To report on the identification of a mutation in glomulin in 23 additional families with GVM.
Results:
Three mutations are new; the others have been described previously. Among the 17 different inherited mutations in glomulin known up to now in 43 families, the 157delAAGAA mutation is the most common and was present in 21 families (48.8%). Mutation 108C-->A was found in five families (11.8%), and the mutations 554delA+556delCCT and 1179delCAA were present together in two families (4.7% each). Polymorphic markers suggested a founder effect for all four mutations.
Conclusions:
Screening for these mutations should lead to a genetic diagnosis in about 70% of patients with inherited GVM. So far, a mutation in glomulin has been found in all GVM families tested, thus demonstrating locus homogeneity.
Insights
Glomuvenous malformation (GVM) is caused by glomulin gene mutations. Identifying these mutations allows for genetic diagnosis in approximately 70% of inherited GVM patients, aiding in understanding this vascular disorder.
Area of Science:
- Genetics
- Dermatology
- Vascular Biology
Background:
- Glomuvenous malformation (GVM), also known as familial glomangioma, is a cutaneous vascular lesion characterized by glomus cells.
- Inherited GVM is associated with chromosome 1p21-22 and caused by mutations in the glomulin gene.
- A double-hit mutation in one lesion suggests GVM results from complete localized loss of glomulin function.
Purpose of the Study:
- To identify glomulin gene mutations in 23 additional families with GVM.
- To expand the understanding of genetic mutations underlying inherited GVM.
Main Methods:
- Genetic analysis of 23 GVM families.
- Mutation screening in the glomulin gene.
- Use of polymorphic markers to investigate founder effects.
Main Results:
- Identified three novel glomulin mutations, adding to previously described ones.
- The 157delAAGAA mutation was the most prevalent, found in 21 families (48.8%).
- Founder effects were suggested for four common glomulin mutations.
Conclusions:
- Genetic screening for glomulin mutations can diagnose approximately 70% of inherited GVM cases.
- All tested GVM families harbored a glomulin mutation, indicating locus homogeneity.
- These findings facilitate genetic diagnosis and understanding of GVM inheritance.
Related Concept Videos
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
02:30Genomic Imprinting and Inheritance
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
01:39Mutations
02:21Cancers Originate from Somatic Mutations in a Single Cell
01:43Sex-linked Disorders
01:33Cancer-Critical Genes I: Proto-oncogenes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...