Significant evidence for linkage of febrile seizures to chromosome 5q14-q15

Febrile seizures (FSs) represent the most common form of childhood seizure. In the Japanese population, the incidence rate is as high as 7%. It has be en recognized that there is a significant genetic component for susceptibil ity to this type of seizure. Two putative FS loci, FEB1 (chromosome 8q13-q2 1) and FEB2 (chromosome 19p), have been mapped. Furthermore, a mutation in the voltage-gated sodium (Na+)-channel beta 1 subunit gene (SCN1B) at chrom osome 19q13.1 was identified in a family with a clinical subset, termed gen eralized epilepsy with febrile seizures plus (GEFS(+)). These loci are link ed to some large families. in this study, we conducted a genome-wide linkag e search for FS in one large family with subsequent linkage confirmation in 39 nuclear families. Significant linkage was found at D5S644 by multipoint non-parametric analysis using GENEHUNTER (P=5.4x10(-6)). Estimated lambda( s) at D5S644 was 2.5 according to maximum likelihood analysis. Significant linkage disequilibria with FS were observed at the markers D5S644, D5S652 a nd D5S2079 in 47 families by transmission disequilibrium tests. These findi ngs indicate that there is a gene on chromosome 5q14-q15 that confers susce ptibility to FSs and we call this gene FEB4.