Thesis (Ph.D.)--Chulalongkorn University, 2011

Benign Adult Familial Myoclonic Epilepsy (BAFME) is a neurogenetic disorder, inherited in an autosomal dominant fashion. Patients usually have cortical tremor or generalized seizure when entering adulthood. It has been mapped to chromosomes 8q23.3-q24.1, 2p11.1-q12.2 and recently 5p15.31-p15. However, there remain families with absence of linkage to these known loci. We studied 24 Thai individuals of the same family. Clinical and electrophysiological studies revealed that 13 had BAFME. Genome-wide linkage study (GWLS) was performed using 400 microsatellite markers. Genotyping with microsatellite markers excluded linkage of the two BAFME loci, 8q23.3-q24.1, 2p11.1-q12.2. GWLS showed that the disease-associated region in our Thai family was linked to a newly identified fourth locus of BAFME on chromosome 3q26.32-3q28. Next-generation sequencing was used to sequence the whole critical region of 18 Mb. In addition, array comparative genomic hybridization was performed to identify copy number variations. Even with both advanced assays, the etiologic gene remains elusive. Discovery of the fourth BAFME chromosomal region will facilitate the identification of the responsible gene. This may provide further understanding into the molecular basis of epilepsy and better insight into the disease mechanism leading to more effective treatment of this disorder.