Related Experiment Videos
Mutations in the gene encoding SLURP-1 in Mal de Meleda.
J Fischer1, B Bouadjar, R Heilig
1Centre National de Génotypage, 91057 Evry, France. fischer@cng.fr
Human Molecular Genetics
|April 4, 2001
Summary
Mal de Meleda (MDM), a rare skin disorder causing palmoplantar keratoderma, is linked to mutations in the SLURP-1 gene. This discovery identifies a secreted protein
Area of Science:
- Genetics
- Dermatology
- Molecular Biology
Background:
- Mal de Meleda (MDM) is a rare autosomal recessive skin disorder.
- Characterized by transgressive palmoplantar keratoderma (PPK), keratotic skin lesions, perioral erythema, brachydactyly, and nail abnormalities.
Purpose of the Study:
- To refine the genetic interval for MDM on chromosome 8qter.
- To identify the specific gene and mutations responsible for MDM.
Main Methods:
- Genetic linkage analysis to refine the MDM locus.
- Mutation screening of candidate genes within the refined interval.
- Analysis of affected individuals from Algerian and Croatian families.
Main Results:
- The MDM locus was refined to chromosome 8qter.
- Mutations in the ARS (component B) gene, encoding secreted Ly-6/uPAR related protein 1 (SLURP-1), were identified in affected individuals.
- Three distinct homozygous mutations (deletion, nonsense, splice site) were found in 19 families, suggesting founder effects and shared haplotypes between Algerian and Croatian populations.
Conclusions:
- Mutations in the SLURP-1 gene are causative for Mal de Meleda.
- This finding implicates a secreted protein, SLURP-1, in the pathogenesis of palmoplantar keratoderma for the first time.
- The study highlights the role of the Ly-6/uPAR superfamily in skin disorders.