MAL de Meleda (MDM) caused by mutations in the gene for SLURP-1 in patients from Germany, Turkey, Palestine, and the United Arab Emirates

Katja Martina Eckl, Howard P. Stevens, Gilles G. Lestringant, Margaretha Westenberger-Treumann, Heiko Traupe, Britta Hinz, Philippe M. Frossard, Rudolf Stadler, Irene M. Leigh, Peter Nürnberg, André Reis, Hans Christian Hennies

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Mal de Meleda (MDM) or keratosis palmoplantaris transgrediens of Siemens is an autosomal recessive skin disorder characterized by diffuse palmoplantar keratoderma (PPK) and transgressive keratosis with an onset in early infancy. There is no associated involvement of other organs; however, a spectrum of clinical presentations with optional and variable features has been described. Mutations in the ARS (component B)-81/s gene (LY6LS) on chromosome 8q24-qter, which encodes SLURP-1, have recently been identified in patients with MDM. Here, we have analyzed four MDM families for mutations in SLURP-1. In a large Palestinian pedigree with multiple consanguinity, patients are homozygous for a new mutation that substitutes an arginine for a conserved glycine residue at position 86. A different mutation in Turkish patients results in the same amino acid exchange. Some remarkable similarities are seen in the clinical picture of patients from both families. Patients of an Emirati Bedouin family have a homozygous alteration of the translation initiation codon. In a German family with no known consanguinity, we have shown pseudodominant inheritance. Three affected children and their affected mother are homozygous for the missense mutation W15R. Our findings indicate that the MDM type of transgressive PPK is caused by SLURP-1 mutations in patients from various origins and demonstrate allelic heterogeneity for mutations in SLURP-1.

Original languageEnglish
Pages (from-to)50-56
Number of pages7
JournalHuman Genetics
Volume112
Issue number1
Early online date19 Oct 2002
DOIs
Publication statusPublished - Jan 2003
Externally publishedYes

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