June 2011

A Novel Homozygous Missense Mutation in SLURP1 Causing Mal de Meleda With an Atypical Phenotype

Author Affiliations

Author Affiliations: Department of Dermatology and Venereology, Innsbruck Medical University, Innsbruck, Austria (Drs Gruber, Romani, and Schmuth); Division of Dermatogenetics, Cologne Center for Genomics, University of Cologne, Cologne, Germany (Dr Hennies).


Copyright 2011 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.2011

Arch Dermatol. 2011;147(6):748-750. doi:10.1001/archdermatol.2011.138

Mal de Meleda (MDM) is a rare autosomal recessive form of keratoderma characterized by sharply demarcated palmoplantar erythema and hyperkeratoses. It usually manifests within the first 2 years of life and takes a slowly progressive course with transgression of the hyperkeratoses to the dorsal aspects of the hands and feet. Associated findings include perioral erythema, hyperkeratotic plaques over the joints, nail abnormalities, hyperhidrosis with malodorous maceration, brachydactyly, and pseudoainhum.13 Mal de Meleda is caused by mutations in SLURP1 (7 different mutations have been detected), encoding the secreted mammalian Ly6/urokinase plasminogen receptor–related protein 1 (SLURP-1), which shows a phylogenetic relationship to snake neurotoxins exhibiting the characteristic 3-finger structure.4 In human keratinocytes, SLURP-1 is an endogenous ligand of the alpha-7-nicotinic acetylcholine receptor and acts as a neuromodulator, likely impacting on epidermal homeostasis and regulating tumor necrosis factor–mediated inflammatory cascades.3

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