Open AccessGenotypes and Phenotypes of 162 Families with a <b><i>Glomulin</i></b> Mutation
Author(s) -
Pascal Brouillard,
Laurence M. Boon,
Nicole Revençu,
Jonathan Berg,
Anne Dompmartin,
Josée Dubois,
Maria C. Garzón,
Simon Holden,
Loshan Kangesu,
Christine Labrèze,
Sally Ann Lynch,
Carole McKeown,
Raimundas Meškauskas,
I. Quéré,
Samira Syed,
P. Vabres,
Michel Wassef,
John B. Mulliken,
Miikka Vikkula
Publication year - 2013
Publication title -
molecular syndromology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.609
H-Index - 36
eISSN - 1661-8777
pISSN - 1661-8769
DOI - 10.1159/000348675
Subject(s) - penetrance , genetics , phenotype , genotype , mutation , expressivity , biology , genotype phenotype distinction , disease , genetic counseling , gene , medicine , pathology
A decade ago, we identified a novel gene, glomulin (GLMN) in which mutations cause glomuvenous malformations (GVMs). GVMs are bluish-purple cutaneous vascular lesions with characteristic glomus cells in the walls of distended venous channels. The discovery of the genetic basis for GVMs allowed the definition of clinical features to distinguish GVMs from other venous anomalies. The variation in phenotype was also highlighted: from a single punctate blue dot to a large plaque-like lesion. In this study, we screened GLMN in a large cohort of patients to broaden the spectrum of mutations, define their frequency and search for possible genotype-phenotype correlations. Taking into account 6 families published by others, a mutation in GLMN has been found in 162 families. This represents 40 different mutations; the most frequent one being present in almost 45% of them. Expressivity varies largely, without a genotype/phenotype relationship. Among 381 individuals with a mutation, we discovered 37 unaffected carriers, implying a penetrance of 90%. As nonpenetrant individuals may transmit the disease to their descendants, knowledge on the mutational status is needed for appropriate genetic counseling.