Genetic analysis of a family with hereditary glomuvenous malformations

Abstract

Glomuvenous malformations (MIM 138000) are rare vascular malformations consisting of glomus cells, and in affected individuals, lesions may appear in any number anywhere on the body. We analysed the DNA of one family with hereditary glomuvenous malformations and identified the mutation causing the disease in the glomulin gene on chromosome 1 p22. The deletion started at base pair 157: 157delAAGAA, which is a deletion of five base pairs. This mutation has been found in Europe, the USA and Australia, suggesting a founder effect with common ancestry. Thus far, no second-hit mutation for the 157delAAGAA mutation has been identified.

The pathobiology of vascular malformations: insights from human and model organism genetics

“…Histological examination reveals dilated veins, lined with endothelial cells that are normal in outward appearance, and the presence of immature VSMCs, termed glomus cells . GVMs are inherited in an autosomal dominant fashion with high penetrance , most lesions developing by the third decade of life . Germline LOF mutations in the glomulin gene have been implicated in GVM pathology .…”

“…GVMs are inherited in an autosomal dominant fashion with high penetrance , most lesions developing by the third decade of life . Germline LOF mutations in the glomulin gene have been implicated in GVM pathology . More recently, Amyere et al confirmed the presence of a second somatic GLMN mutation exclusively within GVM lesions , resulting in a complete loss of glomulin within the affected tissue, thereby explaining the existence of unaffected carriers and the variation in lesion localization.…”

A novel mutation of the glomulin gene in an Italian family with autosomal dominant cutaneous glomuvenous malformations

“…Glomuvenous malformations demonstrate familial aggregation, with autosomal dominant inheritance, and are caused by mutations of the glomulin ( GLMN ) gene mapping to chromosome 1p21‐p22 (8). To our knowledge, GLMN mutations of 49 families have been definitely described (6,8–11). Approximately 50% of GLMN mutations are constituted by the 5‐bp 157delAAGAA deletion, also harboured by the only other Italian family with published genetic test results (8).…”

Genotypes and Phenotypes of 162 Families with a <b><i>Glomulin</i></b> Mutation

“…We mapped the VMGLOM locus on the short arm of chromosome 1, in 1p21p22 [Boon et al, 1999;Brouillard et al, 2000;Irrthum et al, 2001], and identified the causative gene that we named glomulin ( GLMN ) [Brouillard et al, 2002]. We have reported a GLMN mutation in 87 families [Brouillard et al, 2002[Brouillard et al, , 2005[Brouillard et al, , 2008Mallory et al, 2006;Goujon et al, 2011;Butler et al, 2012], and others reported 6 [O'Hagan et al, 2006;Ostberg et al, 2007;Borroni et al, 2011]. The mutations result in loss of function, either by causing a stop codon, by altering the reading frame or by changing the splice-site consensus sequences, leading to aberrant transcripts.…”