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

• Published in: Human genetics 2003, Vol.112 (1), p.50-56
• Main Authors: ECKL, Katja Martina, STEVENS, Howard P, REIS, André, HENNIES, Hans Christian, LESTRINGANT, Gilles G, WESTENBERGER-TREUMANN, Margaretha, TRAUPE, Heiko, HINZ, Britta, FROSSARD, Philippe M, STADLER, Rudolf, LEIGH, Irene M, NÜRNBERG, Peter
• Format: Article
• Language: English
• Subjects: Adult; Amino Acid Substitution; Antigens, Ly - genetics; Arginine - metabolism; Biological and medical sciences; Chromosomes, Human, Pair 8; Classical genetics, quantitative genetics, hybrids; Consanguinity; Dermatology; Dyskeratosis; Female; Fundamental and applied biological sciences. Psychology; Genes, Recessive; Genetic Heterogeneity; Genetics of eukaryotes. Biological and molecular evolution; Germany; Haplotypes; Homozygote; Human; Humans; Infant; Keratoderma, Palmoplantar - complications; Keratoderma, Palmoplantar - etiology; Keratoderma, Palmoplantar - genetics; Keratoderma, Palmoplantar - pathology; Male; Medical sciences; Mutation; Mutation, Missense; Pedigree; Point Mutation; Turkey - ethnology; United Arab Emirates; Urokinase-Type Plasminogen Activator - genetics
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s00439-002-0838-8

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.