Evidence of genetic heterogeneity in families with febrile seizures

Background. Febrile seizures (FS) represent the most common form of childhood seizures. There is a significant genetic component for susceptibility to this type of seizure. Indeed, four putative FS loci, FEB1 (chromosome 8q13-q21), FEB2 (chromosome 19p), FEB3 (chromosome 2q23-24) and FEB4 on chromosome 5q14-15 have been mapped. Purpose. In this study, 10 small families originating in southern Italy that appeared to segregate FS as an autosomal dominant trait were evaluated for linkage to the four known FC loci. Methods. Members of the 12 families were genotyped with microsatellite markers linked to the previously identified febrile convulsion loci, FEB1, FEB2, FEB3 and FEB4. We performed two-point linkage analyses by assuming an autosomal dominant mode of inheritance. Results. In at least two families, significant linkage was found to the FEB3 locus on chromosome 2q. Conclusions. These findings indicate that the FEB3 locus on chromosome 2q confers susceptibility to FS also in some Italian families as well. Our results also illustrate considerable genetic heterogeneity for febrile convulsions.