Mutation screening of three Chinese families with genetic epilepsy with febrile seizures plus.

摘要

Genetic epilepsy with febrile seizures plus (GEFS+) is a familial autosomal dominant condition characterized by genetic heterogeneity. Five genes for GEFS+ identified in large families account for only a small proportion of families. Mutation in the majority of families with GEFS+ has not identified yet. The aim of our study is to search for the gene responsible for GEFS+ in three Chinese families by linkage analyses and a sequencing approach and to investigate the importance of coding and noncoding regions variations of four known GEFS+ genes (SCN1A, SCN1B, GABRG2 and SCN2A) in Chinese families. Results showed that a 6-cM candidate interval at 5q33-34 with a maximum LOD scores of 2.043 was identified in families B. Sequencing candidate gene GABRG2 and GABRA1 in this region did not identify a causative mutation. Moreover, no mutation was found in coding and noncoding regions of the four genes in three Chinese families. Besides excluding coding regions of four known GEFS+ genes, we also excluded the possibility of a mutation in the promoter, exon-intron boundaries, 5' untranslated regions (5' UTRs), and 3' UTRs of four known GEFS+ genes in three Chinese families. In conclusion, the present study demonstrates the heterogeneity of the etiologies of GEFS+. There are as yet undiscovered mechanisms underlying GEFS+.