A locus for febrile seizures (FEB3) maps to chromosome 2q23-24

Abstract

Febrile seizures are the most common form of childhood seizures, occurring in 2% to 5% of North American children. We report a large Utah family with 21 members affected by febrile seizures inherited as an autosomal dominant trait. All had generalized tonic–clonic seizures with onset associated with fever, consistent with the consensus febrile seizure phenotype, and none had febrile seizures beyond 6 years of age. Eighteen affected individuals had recurrent febrile seizures. Eight individuals developed afebrile seizures between ages 5 and 13 years. Afebrile seizures consisted of generalized tonic–clonic, generalized tonic, generalized atonic, simple partial, and partial complex seizure types and were associated with abnormal electroencephalographic findings in 5 individuals, all of whom were intellectually normal. We undertook linkage analysis in this family, defining the disease phenotype as febrile seizures alone. Linkage analysis in epilepsy candidate gene/loci regions failed to show evidence for linkage to febrile seizures. However, a genomewide scan and subsequent fine mapping revealed significant evidence for a new febrile seizure locus (FEB3) on chromosome 2q23‐24 with linkage to the marker D2S2330 (LOD score 8.08 at θ = 0.001). Haplotype analysis defined a critical 10‐cM region between markers D2S141 and D2S2345 that contains the FEB3 locus.

A Missense Mutation of the Gene Encoding Voltage-Dependent Sodium Channel (Nav1.1) Confers Susceptibility to Febrile Seizures in Rats

“…Interestingly, the M145T mutation of SCN1A linked to simple FS was reported on for a large family (Baulac et al, 2004;Mantegazza et al, 2005;Colosimo et al, 2007). This is consistent with other reports that found a link with the FEB3 locus of FS families (Peiffer et al, 1999;Baulac and Baulac, 2009). The phenotypes and genetic conditions of the Hiss rat seem to be very similar to those reported for simple FS patients of the M145T family.…”

Major and minor bio-element status in children with febrile seizure

“…However, FS represents the point between a low seizure threshold and genetic components, recognized to be susceptible for FS and caused by mutations in several gene maps, such as FEB-1 to FEB-4 (5-7). Moreover, some mutations causing neural hyperexcitability could be responsible for FS especially with polygenic multifactorial genetic trait (5,6,8).…”

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.…”