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

Abstract

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 been recognized that there is a significant genetic component for susceptibility to this type of seizure. Two putative FS loci, FEB1 (chromosome 8q13-q21) and FEB2 (chromosome 19p), have been mapped. Furthermore, a mutation in the voltage-gated sodium (Na(+))-channel beta1 subunit gene ( SCN1B ) at chromosome 19q13.1 was identified in a family with a clinical subset, termed generalized epilepsy with febrile seizures plus (GEFS(+)). These loci are linked to some large families. In this study, we conducted a genome-wide linkage 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 = 5.4 x 10(-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 and D5S2079 in 47 families by transmission disequilibrium tests. These findings indicate that there is a gene on chromosome 5q14-q15 that confers susceptibility to FSs and we call this gene FEB4.

Febrile seizures: an update

“…Although there is clear evidence for a genetic basis of FS, the mode of inheritance is unclear. Most convincing evidence has emerged from linkage studies with reported linkages on numerous chromosomes (2q, 48 5q, 49 53 ), with the strongest linkage on chromosome 2q and specifically, linkage to the genes responsible for sodium channel receptors-and specifically a mutation in the alpha (a) subunit of the first neuronal sodium channel gene (SCNIA). The linkage on chromosomes 2q and 19q associated with the phenotype of febrile seizures, generalised epilepsy (tonic-clonic, absence, and myoclonic), and a continuation of febrile seizures (.5 years of age) (GEFS+), 44 54 shows evidence of sodium channel involvement.…”

“…There is currently no evidence that any of these loci have any role in the more common, ''simple'' FS, with the possible exception of the chromosome 5 locus reported in the Japanese population. 49 Clearly, febrile seizures are an extremely heterogeneous condition with a complicated and, as yet, unclear pathophysiological and genetic basis. 55 …”

Novel susceptibility locus at chromosome 6q16.3-22.31 in a family with GEFS+

“…[16][17][18][19][20][21][22][23][24][25][26] Two loci originally described as FS loci (FEB3 and FEB4) were reported in pedigrees best classified as GEFSϩ due to phenotypes beyond typical FS. 20,21,27 Here we describe a GEFSϩ kindred from Central America with evidence for linkage to chromosome 6q16. 3-22.31.…”

Genetische und molekularbiologische Aspekte von Fieberkrämpfen

“…Wallace et al [24] [16]. Unabhängig von dieser Untersuchung gelang erst kürzlich 2 unabhängi-gen Arbeitsgruppen die Identifikation eines Erkrankungsgens in jeweils einer Familie, in denen Fieberkrämpfe im Zusammenhang mit fieberunabhängigen epileptischen Anfällen gehäuft auftraten.…”