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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Generalized arterial calcification of infancy and pseudoxanthoma elasticum can be caused by mutations in either ENPP1 or ABCC6
American Journal of Human Genetics, Volume 90, No. 1, Year 2012
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Description
Spontaneous pathologic arterial calcifications in childhood can occur in generalized arterial calcification of infancy (GACI) or in pseudoxanthoma elasticum (PXE). GACI is associated with biallelic mutations in ENPP1 in the majority of cases, whereas mutations in ABCC6 are known to cause PXE. However, the genetic basis in subsets of both disease phenotypes remains elusive. We hypothesized that GACI and PXE are in a closely related spectrum of disease. We used a standardized questionnaire to retrospectively evaluate the phenotype of 92 probands with a clinical history of GACI. We obtained the ENPP1 genotype by conventional sequencing. In those patients with less than two disease-causing ENPP1 mutations, we sequenced ABCC6. We observed that three GACI patients who carried biallelic ENPP1 mutations developed typical signs of PXE between 5 and 8 years of age; these signs included angioid streaks and pseudoxanthomatous skin lesions. In 28 patients, no disease-causing ENPP1 mutation was found. In 14 of these patients, we detected pathogenic ABCC6 mutations (biallelic mutations in eight patients, monoallelic mutations in six patients). Thus, ABCC6 mutations account for a significant subset of GACI patients, and ENPP1 mutations can also be associated with PXE lesions in school-aged children. Based on the considerable overlap of genotype and phenotype of GACI and PXE, both entities appear to reflect two ends of a clinical spectrum of ectopic calcification and other organ pathologies, rather than two distinct disorders. ABCC6 and ENPP1 mutations might lead to alterations of the same physiological pathways in tissues beyond the artery. © 2012 The American Society of Human Genetics.
Authors & Co-Authors
Baujat, Geneviève
France, Paris
Université Paris Cité
Le Merrer, Martine F.
France, Paris
Université Paris Cité
Lambot-Juhan, Karen
France, Paris
Université Paris Cité
Chassaing, Nicolas
France, Toulouse
Chu de Toulouse
France, Toulouse
Université Toulouse Iii - Paul Sabatier
Roche, Olivier
France, Paris
Université Paris Cité
Deshpande, Charu Mahesh
United Kingdom, London
Guy's and st Thomas' Nhs Foundation Trust
Steinmann, Beat U.
Switzerland, Zurich
Kinderspital Zürich
Martorell, Loreto
Spain, Esplugues de Llobregat
Hospital Sant Joan de Déu Barcelona
Davies, Justin H.
United Kingdom, Cardiff
University of Wales
Kahler, Stephen G.
United States, Little Rock
Arkansas Children's Hospital
McCulloch, Mignon I.
United Kingdom, London
Evelina London Children's Healthcare
Höhne, Wolfgang Ernst
Germany, Berlin
Charité – Universitätsmedizin Berlin
Martin, Ludovic
France, Angers
Chu Angers
Hadj-Rabia, Smaïl
France, Paris
Université Paris Cité
Rutsch, Frank
Germany, Munster
Universitätsklinikum Münster
Statistics
Citations: 244
Authors: 15
Affiliations: 18
Identifiers
Doi:
10.1016/j.ajhg.2011.11.020
ISSN:
15376605
Research Areas
Cancer
Genetics And Genomics
Maternal And Child Health