title: Mutation in the gene for connexin 30.3 in a family with erythrokeratodermia variabilis.
abstract: Erythrokeratodermia variabilis (EKV) is an autosomal dominant keratinization disorder characterized by migratory erythematous lesions and fixed keratotic plaques. All families with EKV show mapping to chromosome 1p34-p35, and mutations in the gene for connexin 31 (Cx31) have been reported in some but not all families. We studied eight affected and three healthy subjects in an Israeli family, of Kurdish origin, with EKV. After having mapped the disorder to chromosome 1p34-p35, we found no mutations in the genes for Cx31, Cx31.1, and Cx37. Further investigation revealed a heterozygous T-->C transition leading to the missense mutation (F137L) in the human gene for Cx30.3 that colocalizes on chromosome 1p34-p35. This nucleotide change cosegregated with the disease and was not found in 200 alleles from normal individuals. This mutation concerns a highly conserved phenylalanine, in the third transmembrane region of the Cx30.3 molecule, known to be implicated in the wall formation of the gap-junction pore. Our results show that mutations in the gene for Cx30.3 can be causally involved in EKV and point to genetic heterogeneity of this disorder. Furthermore, we suggest that our family presents a new type of EKV because of the hitherto unreported association with erythema gyratum repens.
authors.affiliation: Department of Dermatology, University Hospital, CH-1011 Lausanne, Switzerland.
authors.forename: F
authors.initials: F
authors.lastname: Macari
authors.forename: M
authors.initials: M
authors.lastname: Landau
authors.forename: P
authors.initials: P
authors.lastname: Cousin
authors.forename: B
authors.initials: B
authors.lastname: Mevorah
authors.forename: S
authors.initials: S
authors.lastname: Brenner
authors.forename: R
authors.initials: R
authors.lastname: Panizzon
authors.forename: D F
authors.initials: DF
authors.lastname: Schorderet
authors.forename: D
authors.initials: D
authors.lastname: Hohl
authors.forename: M
authors.initials: M
authors.lastname: Huber
mesh_terms: D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D004890:Erythema / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D018740:Genetic Heterogeneity; D008040:Genetic Linkage / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007557:Israel; D007633:Keratins / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D016415:Sequence Alignment
chemical_list: D017630:Connexins; D012333:RNA, Messenger; C076275:connexin 30.3; D007633:Keratins