New mutation c.374C>T and a putative disease-associated haplotype within SCN1B gene in Tunisian families with febrile seizures.

BACKGROUND: Febrile seizures (FSs) relatively represent the most common form of childhood seizures. FSs are not thought of as a true epileptic disease but rather as a special syndrome characterized by its provoking factor (fever) and a typical range of 3 months to 5 years. Although specific genes affecting the majority of FS cases have not been identified yet, several genetic loci for FSs have been reported recently. The aim of this report is to search for the gene responsible for FSs in six affected Tunisian families. METHODS: A microsatellite marker analysis was performed on the known FS and generalized epilepsy with febrile seizures plus (GEFS+) loci. According to the results obtained by statistical analyses for the six studied families and in agreement with the involvement of SCN1B gene in the GEFS+ syndrome in previous studies, SCN1B on GEFS+1 locus was considered as one of the potential candidate genes and was tested for mutations by direct sequencing. RESULTS: A sequencing analysis of the SCN1B gene revealed a novel mutation (c.374G>T) that changed an arginine residue with leucine at position 125 of the protein. We consider that the variation R125L may affect the protein structure and stability by the loss of hydrogen bonding. Two identified single nucleotide polymorphisms that are located in a neighboring hypothetical polyadenylation were assumed to compose a putative disease-associated haplotype. CONCLUSION: Our results support that SCN1B is the gene responsible in one amongst the six FS Tunisian families studied and might contribute to the FS susceptibility for the five others.

Association of calpain-10 polymorphisms with type 2 diabetes in the Tunisian population.

BACKGROUND: Genome-wide analyses of the genetic predisposition to type 2 diabetes mellitus (T2DM) in different isolates and populations have identified regions of interest called non insulin-dependent diabetes mellitus (NIDDM) 1, 2, 3 and 4. At the NIDDM1 locus (2q37.3), calpain-10 (CAPN10) encodes for a ubiquitously expressed protease implicated in the two fundamental pathophysiological aspects of T2DM. This is a report of the results of a study of the association of four CAPN10 polymorphisms with T2DM in the Tunisian population. PARTICIPANTS AND METHODS: A total of 222 T2DM patients with a diabetes duration of 10 years or more and 206 healthy controls were enrolled to analyze the frequency distribution of four CAPN10 polymorphisms (UCSNP-43, UCSNP-19, UCSNP-110 and UCSNP-63) using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in the Tunisian population. We also investigated the association of T2DM with different haplotypes and haplotype combinations. RESULTS: Only the A allele of UCSNP-43 showed an association with T2DM (odds ratio, OR=1.86). We also identified a novel combination of haplotypes (121/221) defined by three polymorphisms (UCNSP-43, -19 and -63) that is associated with an increased risk of T2DM (OR=2.38). CONCLUSION: In this study involving the Tunisian population, we identified genetic variants within CAPN10 that are linked with T2DM and a novel haplotype combination, 121/221, associated with an increased susceptibility to T2DM.