Mrabet et al. (2007) studied the possible association of mutations of the SCN1A, SCN1B and GABRG2 genes with generalized epilepsy with febrile seizure plus (GEFS+) in two unrelated multigenerational Tunisian families affected with GEFS+ spectrum. Screening of the known SCN1B, SCN1A and GABRG2 gene mutations by direct sequencing excluded the involvement of all known published mutations. However, a novel single insertion of a T nucleotide at a heterozygous state within the intron 12 of the SCN1A gene (IVS12-11insT) was identified in two probands and their parents with a possible pathogenic role in the expression of the GEFS+ disease. Mrabet et al. (2007) hypothesized that this mutation may affect the regulatory elements contained in the intron, influence the splicing system or affect the transcription state, and, subsequently, modify the alpha subunit protein. Another hypothesis is that this insertion may be considered as a specific polymorphism for the Tunisian population. The IVS12-11insT variant is situated in the non-coding part and was present in both affected and unaffected individuals. Nevertheless, no data have been published in the literature about this variant in the Tunisian population, suggesting then that this genetic finding could play a role in predisposing subjects to seizures. Mrabet et al. (2007) concluded that the results obtained from this study corroborate the genetic heterogeneity of GEFS+ predominantly in epilepsy patients of different countries and ethnic groups.

Fendri-Kriaa et al. (2009) conducted a gene-association study to depict the molecular basis of GEFS+ in two affected Tunisian families. Statistical analysis pointed to GABRG2 on the GEFS+3 locus and SCN1A on the GEFS+2 locus as potential candidate genes. Sequencing analysis of the SCN1A gene showed a known mutation (c.1811G>A) and a putative disease-associated haplotype in only one family.