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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Mutations in PVRL4, Encoding cell adhesion molecule nectin-4, cause ectodermal dysplasia-syndactyly syndrome
American Journal of Human Genetics, Volume 87, No. 2, Year 2010
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Description
Ectodermal dysplasias form a large disease family with more than 200 members. The combination of hair and tooth abnormalities, alopecia, and cutaneous syndactyly is characteristic of ectodermal dysplasia-syndactyly syndrome (EDSS). We used a homozygosity mapping approach to map the EDSS locus to 1q23 in a consanguineous Algerian family. By candidate gene analysis, we identified a homozygous mutation in the PVRL4 gene that not only evoked an amino acid change but also led to exon skipping. In an Italian family with two siblings affected by EDSS, we further detected a missense and a frameshift mutation. PVRL4 encodes for nectin-4, a cell adhesion molecule mainly implicated in the formation of cadherin-based adherens junctions. We demonstrated high nectin-4 expression in hair follicle structures, as well as in the separating digits of murine embryos, the tissues mainly affected by the EDSS phenotype. In patient keratinocytes, mutated nectin-4 lost its capability to bind nectin-1. Additionally, in discrete structures of the hair follicle, we found alterations of the membrane localization of nectin-afadin and cadherin-catenin complexes, which are essential for adherens junction formation, and we found reorganization of actin cytoskeleton. Together with cleft lip and/or palate ectodermal dysplasia (CLPED1, or Zlotogora-Ogur syndrome) due to an impaired function of nectin-1, EDSS is the second known "nectinopathy" caused by mutations in a nectin adhesion molecule. © 2010 The American Society of Human Genetics.
Authors & Co-Authors
Brancati, Francesco
Italy, Chieti
University of G. D'annunzio Chieti and Pescara
Italy, San Giovanni Rotondo
Irccs Casa Sollievo Della Sofferenza
Fortugno, Paola
Italy, Rome
Irccs Istituto Dermopatico Dell'immacolata
Bottillo, Irene
Italy, San Giovanni Rotondo
Irccs Casa Sollievo Della Sofferenza
Lopez, Marc
France, Paris
Cnrs Centre National de la Recherche Scientifique
Josselin, Emmanuelle
France, Paris
Cnrs Centre National de la Recherche Scientifique
Boudghene-Stambouli, Omar
Algeria, Tlemcen
Université Abou Bekr Belkaid Tlemcen
Agolini, Emanuele
Italy, San Giovanni Rotondo
Irccs Casa Sollievo Della Sofferenza
Bernardini, Laura
Italy, San Giovanni Rotondo
Irccs Casa Sollievo Della Sofferenza
Bellacchio, Emanuele
Italy, San Giovanni Rotondo
Irccs Casa Sollievo Della Sofferenza
Iannicelli, Miriam
Italy, San Giovanni Rotondo
Irccs Casa Sollievo Della Sofferenza
Rossi, Alfredo
Italy, Rome
Sapienza Università Di Roma
Dib-Lachachi, Amina
Algeria, Tlemcen
Université Abou Bekr Belkaid Tlemcen
Stuppìa, Liborio
Italy, Chieti
University of G. D'annunzio Chieti and Pescara
Palka, Giandomenico
Italy, Chieti
University of G. D'annunzio Chieti and Pescara
Mundlos, Stefan
Germany, Berlin
Charité – Universitätsmedizin Berlin
Germany, Berlin
Max Planck Institute for Molecular Genetics
Stricker, Sigmar
Germany, Berlin
Charité – Universitätsmedizin Berlin
Germany, Berlin
Max Planck Institute for Molecular Genetics
Kornak, Uwe
Germany, Berlin
Charité – Universitätsmedizin Berlin
Germany, Berlin
Max Planck Institute for Molecular Genetics
Zambruno, Giovanna
Italy, Rome
Irccs Istituto Dermopatico Dell'immacolata
Dallapiccola, Bruno
Italy, Rome
Irccs Ospedale Pediatrico Bambino Gesù
Statistics
Citations: 101
Authors: 19
Affiliations: 9
Identifiers
Doi:
10.1016/j.ajhg.2010.07.003
ISSN:
00029297
Research Areas
Cancer
Genetics And Genomics
Health System And Policy