Localization of the gene causing keratolytic winter erythema to chromosome 8p22-p23, and evidence for a founder effect in south african afrikaans-speakers

Item Type:	Article
Title:	Localization of the gene causing keratolytic winter erythema to chromosome 8p22-p23, and evidence for a founder effect in south african afrikaans-speakers
Creators Name:	Starfield, M. and Hennies, H.C. and Jung, M. and Jenkins, T. and Wienker, T.F. and Hull, P. and Spurdle, A. and Kuester, W. and Ramsay, M. and Reis, A.
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.
Keywords:	Chromosome Mapping, Dominant Genes, Erythema, Exfoliative Dermatitis, Founder Effect, Genetic Linkage, Germany, Haplotypes, Keratins, Lod Score, Microsatellite Repeats, Pair 8 Human Chromosomes, Palmoplantar Keratoderma, Pedigree, Periodicity, Seasons, South Africa
Source:	American Journal of Human Genetics
ISSN:	0002-9297
Publisher:	University of Chicago Press
Volume:	61
Number:	2
Page Range:	370-378
Date:	August 1997
Official Publication:	https://doi.org/10.1086/514848
PubMed:	View item in PubMed

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