Genome-wide linkage scan for psoriasis susceptibility loci in multiplex Tunisian families.

BACKGROUND: Psoriasis is a relapsing chronic inflammatory skin disease affecting all population groups, with a peak prevalence of 3% in northern European and Scandinavian caucasians. Epidemiological studies have implicated a genetic component to psoriasis. In the past 12 years multiple genome-wide linkage analyses have identified putative susceptibility loci on several chromosomes, with a major locus in the major histocompatibility complex region. OBJECTIVES: To investigate the genetic basis of familial psoriasis in the Tunisian population using a genome-wide linkage scan in seven ultiplex psoriatic families from Tunisia. METHODS: Following single nucleotide polymorphism (SNP) genotyping on the Affymetrix 10K SNP array, we performed nonparametric linkage (NPL) multipoint analyses to identify genotypes and obtain evidence for linkage with psoriasis across the genome. RESULTS: No chromosomal region gave consistent evidence for linkage, providing evidence for genetic heterogeneity in Tunisian psoriasis families. Significant evidence for linkage of psoriasis to chromosome 2p12 was seen in one family. We also identified several regions of tentative psoriasis linkage on chromosomes 2q, 4q, 6p, 11q, 12q, 9q and 13q. One family exhibiting suggestive evidence for linkage to 17q25 (PSORS2) was identified and all affected members harboured a p.Gly117Ser mutation in CARD14 (caspase recruitment domain family, member 14), recently reported to lead to psoriasis in a large family from the U.S.A. CONCLUSIONS: Our results support the genetic heterogeneity of psoriasis in the Tunisian population, provide confirmatory evidence for a novel psoriasis locus at chromosome 2p12 and reveal a psoriasis family with a mutation at PSORS2.

[Familial psoriasis: descriptive report of 9 families]. / Le psoriasis familial: etude descriptive à propos de 9 familles.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease. The familial nature of psoriasis has long been recognized. Aim of our study was to describe the epidemiological, clinical and genetic features of familial psoriasis. METHODS: Through a prospective study we investigated during a study period of lyear (2006-2007) 9 Tunisian unrelated multiplex families. Patients with psoriasis and their available family members were examined by the same dermatologist. RESULTS: Thirty nine individual presented psoriasis (25 men and 4 women), with a mean age at onset about 19.8 years. With the systematic exam of member's family we discover 11 cases of unknown psoriasis. The common form of psoriasis was the preponderant one (37 cases). The nails, the scalp, the mucous membranes were involved respectively in 21, 12 and 13 cases. The psoriasis was severe in 11 cases. CONCLUSION: Through this study we find similar epidemiological and clinical features of those reported previously. The intra and inter-familial variability was evident in our patients.

Comparative clinical and transcriptomal profiles of breast cancer between French and South Mediterranean patients show minor but significative biological differences.

BACKGROUND: In Western countries, breast cancer incidence and mortality are higher than in Mediterranean countries. These differences have been ascribed to environmental factors but also to late-stage diagnostic and biological specific characteristics. PATIENTS AND METHODS: Between September 2002 and September 2005, we collected clinical data by phone counselling 180 French and Mediterranean breast cancer patients and performed microarray experiments. RESULTS: Characteristics of breast cancer in patients from Lebanon, Tunisia and Morocco were more aggressive (more SBR grade III and positive node invasion) and patients were 10 years younger at diagnosis. Sixteen differentially expressed genes such as MMP9, VEGF, PHB1, BRCA1, TFAP2C, GJA1 and TFF1 were also found. Additionally, an up-regulation of cytokeratins KRT8 and KRT18 may indicate a luminal B subtype in "South" (Lebanon, Tunisia and Morocco) tumors while "North" (France) tumors may more frequently be luminal A type. CONCLUSION: This study allowed the identification of specific clinical and transcriptomic parameters in patients from South Mediterranean countries.

Expression of the autoreactive Ig repertoire in a large family, with high prevalence of thyroid autoimmune diseases.

We have investigated the autoreactive Ig repertoire expressed by sera Ig of patients and healthy relatives individuals, who belong to a large family with high prevalence of autoimmune thyroid diseases (AITD). We have used a panel of thyroid, muscular and nuclear self antigens. IgG autoantibodies directed against thyroid antigens were found in 17 out of 29 patients (58.62%) and in 10 out of 46 (21.7%) of relatives sera which suggested that some relatives were either predisposed to develop the AITD or already affected with AITD. IgM natural autoantibodies (NAAb) directed against muscular and nuclear antigens were found in 27 out of 46 (58.69%) of healthy individuals but not exhibited in all of the patients. In relative's sera, the presence of anti-Tg and anti-TPO seems to be associated with the increase of the NAAb activity. Our Data suggested that The emergence of anti-Tg and anti-TPO auto-antibodies is secondary to a polyclonal activation.

Identification of an immunodominant 32-kilodalton membrane protein of Leishmania donovani infantum promastigotes suitable for specific diagnosis of Mediterranean visceral leishmaniasis.

Sera from 35 patients suffering from Mediterranean visceral leishmaniasis (caused by Leishmania donovani infantum) and 59 patients with various forms of cutaneous leishmaniasis prevalent in the sub-Mediterranean countries (caused by Leishmania major, L. donovani infantum, or Leishmania tropica) were tested by immunoblotting and enzyme-linked immunosorbent assay (ELISA) with both membrane and soluble antigens prepared from L. donovani infantum parasites. Control sera were from healthy children (n = 41), adults with nonleishmanial diseases (n = 40), and patients with Chagas' disease (n = 12). A P32 antigen present in the membrane preparation from L. donovani infantum parasites was recognized by 95% of serum specimens from patients with Mediterranean visceral leishmaniasis but not by serum specimens from patients with cutaneous leishmaniasis or sera from control individuals. An ELISA with electroeluted P32 antigen was found to have a specificity and sensitivity of 94% in the serodiagnosis of Mediterranean visceral leishmaniasis. Healthy children with asymptomatic Leishmania infection were seronegative for the P32 antigen by ELISA. These results suggest that antibodies to P32 antigen develop only in patients with visceral leishmaniasis and that the P32 ELISA may be useful in areas where the disease is endemic for discriminating between patients with this disease and those with other clinical conditions.