Festschrift: Professor Jenkins

The elusive gene for keratolytic winter erythema

Peter R Hull, Angela Hobbs, Shaun Aron, Michèle Ramsay

Abstract


Keratolytic winter erythema (KWE), also known as Oudtshoorn skin disease, is characterised by a cyclical disruption of normal epidermal keratinisation affecting primarily the palmoplantar skin with peeling of the palms and soles, which is worse in the winter. It is a rare monogenic, autosomal dominant condition of unknown cause. However, due to a founder effect, it occurs at a prevalence of 1/7 200 among South African Afrikaans-speakers. In the mid-1980s, samples were collected from affected families for a linkage study to pinpoint the location of the KWE gene. A genome-wide linkage analysis, using microsatellite markers, identified the KWE critical region on chromosome 8p23.1-p22. Subsequent genetic studies focused on screening candidate genes in this critical region; however, no pathogenic mutations that segregated exclusively with KWE were identified. The cathepsin B (CTSB) and farnesyl-diphosphate farnesyltransferase 1 (FDFT1) genes revealed no potentially pathogenic variants, nor did they show differential gene expression in affected skin. Mutation detection in additional candidate genes also failed to identify the KWE-associated variant, suggesting that the causal variant may be in an uncharacterised functional region. Bioinformatic analysis revealed highly conserved regions within the KWE critical region and a custom tiling array was designed to cover this region and to search for copy number variation. Although the study did not identify a variant that segregates exclusively with KWE, it provided valuable insight into the complex KWE-linked region. Next-generation sequencing approaches are being used to comb the region, but the causal variant for this interesting hyperkeratotic palmoplantar phenotype still remains elusive. 


Authors' affiliations

Peter R Hull, Division of Dermatology, Department of Medicine, Royal University Hospital, University of Saskatchewan, Canada

Angela Hobbs, Division of Human Genetics, School of Pathology, University of the Witwatersrand, Johannesburg, South Africa

Shaun Aron, Wits Bioinformatics, University of the Witwatersrand, Johannesburg, South Africa

Michèle Ramsay, Division of Human Genetics, School of Pathology and the Sydney Brenner Institute of Molecular Bioscience, University of the Witwatersrand, Johannesburg, South Africa

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Keywords

genetics; keratolytic winter erythema; festschrift; Trefor Jenkins; human genetics

Cite this article

South African Medical Journal 2013;103(12):961-965. DOI:10.7196/SAMJ.7253

Article History

Date submitted: 2013-07-11
Date published: 2013-10-11

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