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Mutations in PVRL4, encoding cell adhesion molecule nectin-4, cause ectodermal dysplasia-syndactyly syndrome.Am J Hum Genet. 2010 Aug 13; 87(2):265-73.AJ
Abstract
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.
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MeSH
Pub Type(s)
Journal Article
Research Support, Non-U.S. Gov't
Language
eng
PubMed ID
20691405
Citation
Brancati, Francesco, et al. "Mutations in PVRL4, Encoding Cell Adhesion Molecule Nectin-4, Cause Ectodermal Dysplasia-syndactyly Syndrome." American Journal of Human Genetics, vol. 87, no. 2, 2010, pp. 265-73.
Brancati F, Fortugno P, Bottillo I, et al. Mutations in PVRL4, encoding cell adhesion molecule nectin-4, cause ectodermal dysplasia-syndactyly syndrome. Am J Hum Genet. 2010;87(2):265-73.
Brancati, F., Fortugno, P., Bottillo, I., Lopez, M., Josselin, E., Boudghene-Stambouli, O., Agolini, E., Bernardini, L., Bellacchio, E., Iannicelli, M., Rossi, A., Dib-Lachachi, A., Stuppia, L., Palka, G., Mundlos, S., Stricker, S., Kornak, U., Zambruno, G., & Dallapiccola, B. (2010). Mutations in PVRL4, encoding cell adhesion molecule nectin-4, cause ectodermal dysplasia-syndactyly syndrome. American Journal of Human Genetics, 87(2), 265-73. https://doi.org/10.1016/j.ajhg.2010.07.003
Brancati F, et al. Mutations in PVRL4, Encoding Cell Adhesion Molecule Nectin-4, Cause Ectodermal Dysplasia-syndactyly Syndrome. Am J Hum Genet. 2010 Aug 13;87(2):265-73. PubMed PMID: 20691405.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR
T1 - Mutations in PVRL4, encoding cell adhesion molecule nectin-4, cause ectodermal dysplasia-syndactyly syndrome.
AU - Brancati,Francesco,
AU - Fortugno,Paola,
AU - Bottillo,Irene,
AU - Lopez,Marc,
AU - Josselin,Emmanuelle,
AU - Boudghene-Stambouli,Omar,
AU - Agolini,Emanuele,
AU - Bernardini,Laura,
AU - Bellacchio,Emanuele,
AU - Iannicelli,Miriam,
AU - Rossi,Alfredo,
AU - Dib-Lachachi,Amina,
AU - Stuppia,Liborio,
AU - Palka,Giandomenico,
AU - Mundlos,Stefan,
AU - Stricker,Sigmar,
AU - Kornak,Uwe,
AU - Zambruno,Giovanna,
AU - Dallapiccola,Bruno,
PY - 2010/04/18/received
PY - 2010/06/28/revised
PY - 2010/07/08/accepted
PY - 2010/8/10/entrez
PY - 2010/8/10/pubmed
PY - 2010/9/2/medline
SP - 265
EP - 73
JF - American journal of human genetics
JO - Am J Hum Genet
VL - 87
IS - 2
N2 - 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.
SN - 1537-6605
UR - https://wwww.unboundmedicine.com/medline/citation/20691405/Mutations_in_PVRL4_encoding_cell_adhesion_molecule_nectin_4_cause_ectodermal_dysplasia_syndactyly_syndrome_
L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002-9297(10)00359-9
DB - PRIME
DP - Unbound Medicine
ER -
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