Genetic Heterogeneity in Keratolytic Winter Erythema (Oudtshoorn Skin Disease)

Huntington, Mark K; Jassim, Ali

doi:10.1001/archderm.142.8.1073

Cited by 11 publications

(5 citation statements)

References 3 publications

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“…Keratolytic winter erythema (KWE) is a rare autosomal dominant condition mostly occurring among South African Afrikaans‐speaking Caucasoid populations of the Eastern Cape and Oudtshoorn districts. It has also been described in British and American families with South African or Norwegian ancestors as well as in Germany and Denmark . The KWE critical region has been mapped to chromosome 8p23.1‐p22 .…”

Section: Isolated Palmoplantar Keratodermasmentioning

confidence: 99%

Hereditary palmoplantar keratodermas. Part I. Non‐syndromic palmoplantar keratodermas: classification, clinical and genetic features

Guerra

Castori

Didona

et al. 2018

Acad Dermatol Venereol

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The term palmoplantar keratoderma (PPK) indicates any form of persistent thickening of the epidermis of palms and soles and includes genetic as well as acquired conditions. We review the nosology of hereditary PPKs that comprise an increasing number of entities with different prognoses, and a multitude of associated cutaneous and extracutaneous features. On the basis of the phenotypic consequences of the underlying genetic defect, hereditary PPKs may be divided into the following: (i) non-syndromic, isolated PPKs, which are characterized by a unique or predominant palmoplantar involvement; (ii) non-syndromic PPKs with additional distinctive cutaneous and adnexal manifestations, here named complex PPKs; (iii) syndromic PPKs, in which PPK is associated with specific extracutaneous manifestations. To date, the diagnosis of the different hereditary PPKs is based mainly on clinical history and features combined with histopathological findings. In recent years, the exponentially increasing use of next-generation sequencing technologies has led to the identification of several novel disease genes, and thus substantially contributed to elucidate the molecular basis of such a heterogeneous group of disorders. Here, we focus on hereditary non-syndromic isolated and complex PPKs. Syndromic PPKs are reviewed in the second part of this 2-part article, where other well-defined genetic diseases, which may present PPK among their phenotypic manifestations, are also listed and diagnostic and therapeutic approaches for PPKs are summarized.

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Section: Isolated Palmoplantar Keratodermasmentioning

confidence: 99%

Hereditary palmoplantar keratodermas. Part I. Non‐syndromic palmoplantar keratodermas: classification, clinical and genetic features

Guerra

Castori

Didona

et al. 2018

Acad Dermatol Venereol

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“…However the precise gene has yet to be identified 5 . A recent study in a Norwegian family failed to detect a common haplotype in affected members for the 8p22–p23 region using linkage studies for two markers, suggesting genetic heterogeneity 8 …”

Section: Reportmentioning

confidence: 99%

“…5 A recent study in a Norwegian family failed to detect a common haplotype in affected members for the 8p22-p23 region using linkage studies for two markers, suggesting genetic heterogeneity. 8 Treatments are often unsatisfactory. Topical steroids and retinoids have been tried with little effect, 6 and in some cases topical steroids can actually worsen the skin disease.…”

Section: Figurementioning

confidence: 99%

Keratolytic winter erythema with facial involvement: a novel presentation

DeGiovanni

Farrant

Howell

et al. 2009

Clinical and Experimental Dermatology

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We present a 23-year-old woman with a diagnosis of keratolytic winter erythema (erythrokeratolysis hiemalis), who developed facial lesions following a traumatic experience. This rare genodermatosis usually affects the palms and soles, and appears as mild erythema and annular scaling. The limbs and trunk can rarely be affected. To our knowledge, this is the first reported case of facial involvement.

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“…All KWE-affected families in South Africa can be traced back to Captain Francois Renier Duminy (born in Lorient, France, in 1747), pointing to a founder effect as the cause of the high prevalence (1/7,200) of KWE in white Afrikaans speakers. 3 KWE has also been described in Germany, 4 Denmark, 5 the US (in a family of Norwegian descent), 6 and the UK (in a family linked to the South African pedigrees). 7 Genome-wide linkage analysis in South African families and one German family mapped the disease locus to chromosomal region 8p23.1-22 from marker D8S1759 to D8S552.…”

Section: Introductionmentioning

confidence: 97%

Duplicated Enhancer Region Increases Expression of CTSB and Segregates with Keratolytic Winter Erythema in South African and Norwegian Families

Ngcungcu

Oti

Sitek

et al. 2017

The American Journal of Human Genetics

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Keratolytic winter erythema (KWE) is a rare autosomal-dominant skin disorder characterized by recurrent episodes of palmoplantar erythema and epidermal peeling. KWE was previously mapped to 8p23.1-p22 (KWE critical region) in South African families. Using targeted resequencing of the KWE critical region in five South African families and SNP array and whole-genome sequencing in two Norwegian families, we identified two overlapping tandem duplications of 7.67 kb (South Africans) and 15.93 kb (Norwegians). The duplications segregated with the disease and were located upstream of CTSB, a gene encoding cathepsin B, a cysteine protease involved in keratinocyte homeostasis. Included in the 2.62 kb overlapping region of these duplications is an enhancer element that is active in epidermal keratinocytes. The activity of this enhancer correlated with CTSB expression in normal differentiating keratinocytes and other cell lines, but not with FDFT1 or NEIL2 expression. Gene expression (qPCR) analysis and immunohistochemistry of the palmar epidermis demonstrated significantly increased expression of CTSB, as well as stronger staining of cathepsin B in the stratum granulosum of affected individuals than in that of control individuals. Analysis of higher-order chromatin structure data and RNA polymerase II ChIA-PET data from MCF-7 cells did not suggest remote effects of the enhancer. In conclusion, KWE in South African and Norwegian families is caused by tandem duplications in a non-coding genomic region containing an active enhancer element for CTSB, resulting in upregulation of this gene in affected individuals.

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Genetic Heterogeneity in Keratolytic Winter Erythema (Oudtshoorn Skin Disease)

Cited by 11 publications

References 3 publications

Hereditary palmoplantar keratodermas. Part I. Non‐syndromic palmoplantar keratodermas: classification, clinical and genetic features

Hereditary palmoplantar keratodermas. Part I. Non‐syndromic palmoplantar keratodermas: classification, clinical and genetic features

Keratolytic winter erythema with facial involvement: a novel presentation

Duplicated Enhancer Region Increases Expression of CTSB and Segregates with Keratolytic Winter Erythema in South African and Norwegian Families

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