Localization of the Gene Causing Keratolytic Winter Erythema to Chromosome 8p22-p23, and Evidence for a Founder Effect in South African Afrikaans-Speakers

Michelle Starfield, Hans Christian Hennies, Martin Jung, Trefor Jenkins, Thomas Wienker, Peter Hull, Amanda Spurdle, Wolfgang Küster, Michele Ramsay, André Reis

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Keratolytic winter erythema (KWE), also known as “Oudts-hoorn 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 (Zmax) of 9.2 at a maximum recombination fraction (θmax) of .0 in the German family. Linkage was also demonstrated in five of the larger South African families, with Zmax = 7.4 at θmax = .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.
Original languageEnglish
Pages (from-to)370-378
Number of pages9
JournalAmerican Journal of Human Genetics
Volume61
Issue number2
DOIs
Publication statusPublished - Aug 1997
Externally publishedYes

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