RT Journal Article
SR Electronic
T1 Four common glomulin mutations cause two thirds of glomuvenous malformations (“familial glomangiomas”): evidence for a founder effect
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP e13
OP e13
DO 10.1136/jmg.2004.024174
VO 42
IS 2
A1 P Brouillard
A1 M Ghassibé
A1 A Penington
A1 L M Boon
A1 A Dompmartin
A1 I K Temple
A1 M Cordisco
A1 D Adams
A1 F Piette
A1 J I Harper
A1 S Syed
A1 F Boralevi
A1 A Taïeb
A1 S Danda
A1 E Baselga
A1 O Enjolras
A1 J B Mulliken
A1 M Vikkula
YR 2005
UL http://jmg.bmj.com/content/42/2/e13.abstract
AB 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.