Four common glomulin mutations cause two thirds of glomuvenous malformations (“familial glomangiomas”): evidence for a founder effect
- P Brouillard1,
- M Ghassibé1,
- A Penington2,
- L M Boon3,
- A Dompmartin4,
- I K Temple5,
- M Cordisco6,
- D Adams7,
- F Piette8,
- J I Harper9,
- S Syed9,
- F Boralevi10,
- A Taïeb10,
- S Danda11,*,
- E Baselga12,
- O Enjolras13,
- J B Mulliken14,
- M Vikkula1
- 1Laboratory of Human Molecular Genetics, Christian de Duve Institute of Cellular Pathology and Université catholique de Louvain, Brussels, Belgium
- 2University of Melbourne, Department of Surgery, St Vincent’s Hospital, Melbourne, Australia
- 3Centre of Vascular Anomalies, Division of Plastic Surgery, Université catholique de Louvain, Brussels, Belgium
- 4Dermatologie, Centre Hospitalier Universitaire, Caen, France
- 5Wessex Clinical Genetics Service and Division of Human Genetics, Southampton University and Hospital NHS Trust, Southampton, UK
- 6Hospital Nacional de Pediatria, Buenos Aires, Argentina
- 7Department of Pediatrics, Children’s Hospital Medical Center, University of Cincinnati, Ohio, USA
- 8Clinique de Dermatologie, Centre Hospitalier Regional Universitaire, Lille, France
- 9Great Ormond Street Hospital for Children NHS Trust, London, UK
- 10Unité de Dermatologie Pédiatrique, Hôpital Pellegrin-Enfants, CHU, Bordeaux, France
- 11South Australian Clinical Genetics Service, Women’s & Children’s Hospital, North Adelaide, South Australia
- 12Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain
- 13Consultations des Angiomes, Hôpital Lariboisière, Paris, France
- 14Division of Plastic Surgery, Vascular Anomalies Center, Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
- Correspondence to: Professor Miikka Vikkula Laboratory of Human Molecular Genetics, Christian de Duve Institute of Cellular Pathology and Université catholique de Louvain, Avenue Hippocrate 74, BP 75.39, B-1200 Brussels, Belgium; vikkulabchm.ucl.ac.be
- Received 20 August 2004
- Accepted 23 August 2004
Abstract
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.
Footnotes
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↵* Dr S Danda’s current address: Wellcome Research Unit, Christian Medical College Hospital, Vellore, Tamil Nadu, India
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Conflicts of interest: none declared
