LOCALIZATION OF THE GENE CAUSING KERATOLYTIC WINTER ERYTHEMA TO CHROMOSOME 8P22-P23, AND EVIDENCE FOR A FOUNDER EFFECT IN SOUTH-AFRICAN AFRIKAANS-SPEAKERS

Kerarolytic winter erythema (KWE), also known as ''Oudtshoorn skin dis ease,'' or ''erythrokeratolysis hiemalis,'' is an autosomal dominant s kin disorder of unknown etiology characterized by a cyclical erythema, hyperkeratosis, and recurrent and intermittent peeling of the palms a nd soles, particularly during winter. Initially KWE,was believed to be unique to South Africa, but recently a large pedigree of German origi n has been identified. The disorder occurs with a prevalence of 1/7,00 0 in the South African Africaans-speaking Caucasoid population, and th is high frequency has been attributed to founder effect. After a numbe r of candidate regions were excluded from linkage to KWE in both the G erman family and several South African families, a genomewide analysis was embarked on. Linkage to the microsatellite marker D8S550 on chrom osome 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 th e German family. Linkage was also demonstrated in five of the larger S outh African families, with Z(max) = 7.4 at theta(max) = .02. When hap lotypes were constructed, 11 of 14 South African KWE families had the complete ''ancestral'' haplotype, and 3 demonstrated conservation of p arts of this haplotype, supporting the hypothesis of founder effect, T he chromosome segregating with the disease in the German family demons trated 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. HE it is assumed that there was a single South African founder, a proposed ancestral recombinant sugg ests that the gene is most likely in a 1-cM interval between D8S550 an d D8S265.