Mutation analysis in Irish families with glomuvenous malformations

Abstract

Summary Background Glomuvenous malformations (GVMs) are rare bluish lesions that can affect the skin and mucosal surfaces. They represent defects in vasculogenesis. Lesions can occur sporadically or in an autosomal dominant mode of inheritance. Recent studies have shown that mutations in the glomulin gene (GLMN) on chromosome 1p21‐22 are responsible for familial GVMs. Objectives To search for mutations in GLMN in Irish families with GVMs. Methods We identified four Irish families with GVMs and confirmed linkage to chromosome 1p21‐22 in these cases. We sequenced the glomulin gene in all affected and unaffected members of the families. Results Linkage analysis showed that affected individuals from the families shared a common haplotype. Mutation analysis revealed a delAAGAA mutation in exon 3 of the glomulin gene in all four families with GVMs. Conclusions We confirm that mutations in the glomulin gene are responsible for GVMs and suggest a founder Irish mutation in the glomulin gene in four Irish families.

Glomuvenous Malformation in a Boy with Transposition of the Great Vessels: A Case Report and Review of Literature

“…If lesions are extensive, surgical resections become impractical. Sclerotherapy with sodium chloride and sodium tetradecolecylsulfate, electron bean radiation, argon, and carbon dioxide lasers have been attempted with variable success rates in treating extensive GVM (29–35). Treatment of large, extensive and disfiguring lesions remains difficult.…”

“…To this date, there have been 17 different glomulin mutations identified in 43 GVM families tested by Brouillard et al as summarized in Table 2 (11). Interestingly, O’Hagan et al also studied four separate Irish families with GVM and found that all four families had the most common mutation‐ 157delAAGAA (29). There have been no genotype–phenotype associations, and the position of a specific glomulin mutation does not correlate with clinical findings such as location, extent and number of lesions.…”

Vascular Anomalies: From Genetics toward Models for Therapeutic Trials

“…Of the more than 30 mutations identified in more than 100 families, 11 account for .80% of patients (Brouillard, et al 2002(Brouillard, et al , 2005(Brouillard, et al , 2008O'Hagan et al 2006;P Brouillard, LM Boon, JB Mullikan, et al, unpubl.). The identification of the first somatic second-hit in a vascular anomaly, a 5-bp deletion in glomulin, provided evidence for a paradominant mode of inheritance (Brouillard et al 2002).…”

Corrigenda

“…In the above mentioned article 3 there was an error in the author listing. F. Maloney should have appeared as follows:…”