title: Localization of the gene causing keratolytic winter erythema to chromosome 8p22-p23, and evidence for a founder effect in South African Afrikaans-speakers.
abstract: Keratolytic winter erythema (KWE), also known as "Oudtshoorn skin disease," or "erythrokeratolysis hiemalis," is an autosomal dominant skin disorder of unknown etiology characterized by a cyclical erythema, hyperkeratosis, and recurrent and intermittent peeling of the palms and soles, particularly during winter. Initially KWE was believed to be unique to South Africa, but recently a large pedigree of German origin has been identified. The disorder occurs with a prevalence of 1/7,000 in the South African Afrikaans-speaking Caucasoid population, and this high frequency has been attributed to founder effect. After a number of candidate regions were excluded from linkage to KWE in both the German family and several South African families, a genomewide analysis was embarked on. Linkage to the microsatellite marker D8S550 on chromosome 8p22-p23 was initially observed, with a maximum LOD score (Z(max)) of 9.2 at a maximum recombination fraction (theta(max)) of .0 in the German family. Linkage was also demonstrated in five of the larger South African families, with Z(max) = 7.4 at theta(max) = .02. When haplotypes were constructed, 11 of 14 South African KWE families had the complete "ancestral" haplotype, and 3 demonstrated conservation of parts of this haplotype, supporting the hypothesis of founder effect. The chromosome segregating with the disease in the German family demonstrated a different haplotype, suggesting that these chromosomes do not have a common origin. Recombination events place the KWE gene in a 6-cM interval between D8S550 and D8S552. If it is assumed that there was a single South African founder, a proposed ancestral recombinant suggests that the gene is most likely in a 1-cM interval between D8S550 and D8S265.
authors.affiliation: Department of Human Genetics, School of Pathology, South African Institute for Medical Research and University of the Witwatersrand, Johannesburg.
authors.forename: M
authors.initials: M
authors.lastname: Starfield
authors.forename: H C
authors.initials: HC
authors.lastname: Hennies
authors.forename: M
authors.initials: M
authors.lastname: Jung
authors.forename: T
authors.initials: T
authors.lastname: Jenkins
authors.forename: T
authors.initials: T
authors.lastname: Wienker
authors.forename: P
authors.initials: P
authors.lastname: Hull
authors.forename: A
authors.initials: A
authors.lastname: Spurdle
authors.forename: W
authors.initials: W
authors.lastname: Küster
authors.forename: M
authors.initials: M
authors.lastname: Ramsay
authors.forename: A
authors.initials: A
authors.lastname: Reis
mesh_terms: D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D003873:Dermatitis, Exfoliative / Q000453:epidemiology / Q000235:genetics*; D004890:Erythema / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D005799:Genes, Dominant; D008040:Genetic Linkage; D005858:Germany / Q000453:epidemiology / Q000208:ethnology; D006239:Haplotypes; D006801:Humans; D007633:Keratins / Q000235:genetics; D007645:Keratoderma, Palmoplantar / Q000453:epidemiology / Q000235:genetics*; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree; D010507:Periodicity; D012621:Seasons; D013019:South Africa / Q000453:epidemiology
chemical_list: D007633:Keratins