A novel genetic locus for familial febrile seizures and epilepsy on chromosome 3q26.2–q26.33

Abstract

Febrile seizures (FS) are common in children, and the incidence is 2-5% before the age of 5 years. A four-generation Chinese family with autosomal dominant febrile seizure and epilepsy was studied by genome-wide linkage analysis. Significant linkage was identified with markers on chromosome 3q26.2-26.33 with a maximum pairwise LOD score of >3.00. Fine mapping defined the new genetic locus within a 10.7-Mb region between markers D3S3656 and D3S1232. A maximum multipoint LOD score of 5.27 was detected at marker D3S1565. A previously reported CLCN2 gene for epilepsy was excluded as the disease-causing gene in the family by mutational analysis of all exons and exon-intron boundaries of CLCN2 and by haplotype analysis. Mutation analysis of KCNMB2 and KCNMB3, which were two potassium-channel genes in this linkage region, did not reveal a disease causing mutation. Our results identified another novel locus on chromosome 3q26.2-26.33, and future studies of the candidate genes at the locus will identify a new gene for combined FS and idiopathic epilepsies.

Identification of a novel genetic locus on chromosome 8p21.1–q11.23 for idiopathic basal ganglia calcification

“…Genotypes were analyzed using the GeneMapper 2 Software program (ABI). Two‐point linkage analysis was performed using MLINK as previously described [Dai et al, 2008; Liu et al, 2008]. The assumptions for linkage analysis include a gene frequency of 0.001, a penetrance rate of 95%, a phenocopy rate of 0%, and an allele frequency of 1/n, where n equals the number of alleles observed.…”

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

“…4,15 In addition, linkage studies have identified 7 genomic regions likely to harbor genes increasing risk for GEFSϩ and 5 regions likely to harbor genes increasing risk for FS (table 1). [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.…”

Evaluation of Candidate Genes from Orphan FEB and GEFS+ Loci by Analysis of Human Brain Gene Expression Atlases

“…Dai et al [63] mapped the FEB10 locus in a four-generation Chinese family with autosomal dominant febrile seizures and epilepsy. By mutational analysis, they have excluded the two potassium channel genes KCNMB2 and KCNMB3 , none of which ranks among the top five in our analysis (average relative rank over HBA and GEO).…”