Mutations in the human connexin gene GJB3 cause erythrokeratodermia variabilis

Details

Serval ID
serval:BIB_475B45B48595
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Mutations in the human connexin gene GJB3 cause erythrokeratodermia variabilis
Journal
Nature Genetics
Author(s)
Richard  G., Smith  L. E., Bailey  R. A., Itin  P., Hohl  D., Epstein, E. H., Jr. , DiGiovanna  J. J., Compton  J. G., Bale  S. J.
ISSN
1061-4036 (Print)
Publication state
Published
Issued date
12/1998
Volume
20
Number
4
Pages
366-9
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Dec
Abstract
Erythrokeratodermia variabilis (EKV, OMIM 133200) is an autosomal dominant genodermatosis with considerable intra- and interfamilial variability. It has a disfiguring phenotype characterized by the independent occurrence of two morphologic features: transient figurate red patches and localized or generalized hyperkeratosis. Both features can be triggered by external factors such as trauma to the skin. After initial linkage to the RH locus on 1p, EKV was mapped to an interval of 2.6 cM on 1p34-p35, and a candidate gene (GJA4) encoding the gap junction protein alpha-4 (connexin 31, Cx31) was excluded by sequence analysis. Evidence in mouse suggesting that the EKV region harbours a cluster of epidermally expressed connexin genes led us to characterize the human homologues of GJB3 (encoding Cx31) and GJB5 (encoding Cx31.1). GJB3, GJB5 and GJA4 were localized to a 1.1-Mb YAC in the candidate interval. We detected heterozygous missense mutations in GJB3 in four EKV families leading to substitution of a conserved glycine by charged residues (G12R and G12D), or change of a cysteine (C86S). These mutations are predicted to interfere with normal Cx31 structure and function, possibly due to a dominant inhibitory effect. Our results implicate Cx31 in the pathogenesis of EKV, and provide evidence that intercellular communication mediated by Cx31 is crucial for epidermal differentiation and response to external factors.
Keywords
Amino Acid Sequence Base Sequence Chromosomes, Human, Pair 1 Connexins/*genetics Erythema/*genetics Female Humans Linkage (Genetics) Male Molecular Sequence Data *Mutation Pedigree Sequence Homology, Amino Acid
Pubmed
Web of science
Create date
25/01/2008 16:35
Last modification date
20/08/2019 13:53
Usage data