Linkage studies in erythrokeratodermias: fine mapping, genetic heterogeneity and analysis of candidate genes

Détails

ID Serval
serval:BIB_59AB6575BA0A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Linkage studies in erythrokeratodermias: fine mapping, genetic heterogeneity and analysis of candidate genes
Périodique
Journal of Investigative Dermatology
Auteur(s)
Richard  G., Lin  J. P., Smith  L., Whyte  Y. M., Itin  P., Wollina  U., Epstein, E., Jr. , Hohl  D., Giroux  J. M., Charnas  L., Bale  S. J., DiGiovanna  J. J.
ISSN
0022-202X (Print)
Statut éditorial
Publié
Date de publication
11/1997
Volume
109
Numéro
5
Pages
666-71
Notes
Journal Article --- Old month value: Nov
Résumé
Erythrokeratodermias are a clinically heterogeneous group of rare autosomal dominant disorders of cornification with overlapping features including hyperkeratosis and erythema. We ascertained five extended pedigrees with different phenotypes for a linkage study. Three families presented with localized erythrokeratodermia variabilis, and one with erythrokeratodermia and ataxia. Another family had Greither disease associated with variable hyperkeratotic plaques. Despite their phenotypic differences, both erythrokeratodermia variabilis and erythrokeratodermia with ataxia map to a common region in 1p34-p35. Multipoint linkage and haplotype analyses place erythrokeratodermia variabilis between the marker D1S496 and D1S186 with a maximum LOD score of 12.88. Our linkage results provide compelling evidence for genetic homogeneity among families of mixed European and French-Canadian origin. In contrast, results excluded Greither's disease from the established erythrokeratodermia variabilis gene region indicating genetic heterogeneity of erythrokeratodermias. Based on recombinations, two genes assigned to 1p34-p35 were excluded: cartilage matrix protein and avian myelocytosis viral oncogene. Connexin-37 (GJA4), a member of the connexin gene family, maps within the erythrokeratodermia variabilis region and is an attractive candidate gene. Direct sequencing of the coding region of GJA4 in four patients revealed several variations, including a novel polymorphism within the 5' cytoplasmic domain, but no pathogenic mutations were found, thus excluding Connexin-37 as a candidate. There is evidence, however, that other epidermally expressed connexins cluster in this region, and one may yet be determined to play a role in the pathogenesis of erythrokeratodermia variabilis.
Mots-clé
Chromosome Mapping Chromosomes, Human, Pair 1/genetics Connexins/genetics Erythema/*genetics Genes/genetics Genetic Heterogeneity Haplotypes Humans Hyperpigmentation/*genetics Keratosis/*genetics Linkage (Genetics) Pedigree Phenotype
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/01/2008 17:35
Dernière modification de la notice
20/08/2019 15:13
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