[Linkage location and mutation analysis of generalized epilepsy with febrile seizures plus]

To study the etiologic genes of generalized epilepsy with febrile seizure plus (GEFS+).

Peripheral blood samples were collected from 25 persons of 2 families, including 2 probands. DNA was extracted from the peripheral blood leukocytes using phenol-chloroform method. Ten microsatellite markers spanning the critical regions of SCN1B, SCN1A, SCN2A, and GABRG2 genes were genotyped for linkage analysis by the software LINKAGE v5.1. The two-point linkage relation was determined by LOD score defining the approximate position of etiologic genes of the 2 GEFS+ families. Mutation analysis of the candidate etiologic genes in all members of these 2 families was performed. Results No sharing allele was discovered among the several microsatellite markers flanking SCN1A, SCN2A, and SCN1B genes, and the involvement of these genes in these 2 families could be excluded. In the family named Tian, sharing alleles were discovered among the markers D5S820, D5S422, and D5S1403 flanking GABRG2 gene. The two-point LOD scores at theta = 0 were 0.67, 1.0, and 0.79 for the marker D5S820, D5S422, and D5S1403, thus indicating possible linkage. In the family named Di, sharing allele was discovered only in the marker D5S1403 flanking the GABRG2 gene. Sequence analysis was performed for nine exons of the GABRG2 gene in these 2 families. Three single nucleotide variations were discovered on the exon 5 (c.588 C > T), exon 3 (c.604 C > T), and noncoding region of the exon 7. No mutation change of the GABRG2 gene was observed in these 2 families.

No evidence supports the causal relation between the SCN1B, SCN1A, SCN2A, and GABRG2 mutation and the etiologic genes in the two families with GEFS+. It is still not clear what is the common etiologic genes of GEFS+.