Mutations in the gene encoding SLURP-1 in Mal de Meleda.

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. We report the refinement of our previously described interval of MDM on chromosome 8qter, and the identification of mutations in affected individuals in the ARS (component B) gene, encoding a protein named SLURP-1, for secreted Ly-6/uPAR related protein 1. This protein is a member of the Ly-6/uPAR superfamily, in which most members have been localized in a cluster on chromosome 8q24.3. The amino acid composition of SLURP-1 is homologous to that of toxins such as frog cytotoxin and snake venom neurotoxins and cardiotoxins. Three different homozygous mutations (a deletion, a nonsense and a splice site mutation) were detected in 19 families of Algerian and Croatian origin, suggesting founder effects. Moreover, one of the common haplotypes presenting the same mutation was shared by families from both populations. Secreted and receptor proteins of the Ly-6/uPAR superfamily have been implicated in transmembrane signal transduction, cell activation and cell adhesion. This is the first instance of a secreted protein being involved in a PPK.

[Xeroderma pigmentosum. A study in 40 Algerian patients]. / Xeroderma pigmentosum. Etude de 40 malades algériens.

INTRODUCTION: Xeroderma pigmentosum (XP) is a rate autosomal recessive disorder related to DNA repair defects. Recently, modifications of oncogenes and mutations of the p53 suppressor gene have been reported in skin tumors of XP patients. The purpose is to study, through a series of 40 patients admitted to the Dermatologic Clinic of Algiers, the characteristics of XP in Algeria. PATIENTS AND METHODS: For each patient, familiarity, clinical and biological examinations and therapeutic results were studied. Biological studies have been axed mainly on analysis of DNA extracted from skin tumors of 18 patients to detect oncogene modifications by Southern blot and hybridization. A technic, based on single strand DNA conformation polymorphism (SSCP), has been carried out to detect rapidly mutations on the p53 gene. RESULTS: A consanguinity in the first degree is noted in 95 p. 100 of cases and a familiarity in 63 p. 100 of cases. The median age of patients is 10 years; sex ratio is close to one; 32 patients (80 p. 100) are classic XP and 8 (20 p. 100) are XP variant. In 18 tumors analysed, the Ha-ras gene is amplified and/or modified in 50 p. 100 of cases. Only 3 tumors (16.6 p. 100) show mutations of the p53 gene (transitions C-T). Surgical treatment isolated or associated to polychemotherapy permitted to resolve tumors in 75 p. 100 of cases. DISCUSSION: In Algeria, XP are mainly classic with a particularly high frequency of occular (62 p. 100) and neurological manifestations (62 p. 100). Genetic studies confirm modifications of the Haras gene in direct relation with unrepaired UV lesions in classic XP and mutations of the p53 tumor suppressor gene characteristic of mutation spectra induced by UV. Surgery is the treatment of choice for tumors; polychemotherapy is an alternative in advanced cases.

[Lupoid leishmaniasis]. / Leishmaniose lupoïde.

INTRODUCTION: Due to the wide variety of clinical pictures, several terms have been used in the literature reporting cases of lupoid leishmaniasis, including chronic leishmaniasis and recurrent leishmaniasis. CASES: We report three new cases, two of which presented the classical features, and a third one with an unusual distribution of the lesions. DISCUSSION: Lupoid leishmaniasis is a particular evolving form of cutaneous leishmaniasis with characteristic spreading of the initial nodule, leading to a plaque simulating discoid lupus. Leishmaniasis major was identified in all three patients and recognized as the zoonotic leishmaniasis which usually presents as a classical oriental sore. A clinical course to lupoid leishmaniasis is probably related to changes in cell-mediated immunity leading to localized or diffuse lesions.