Clinical Study and Molecular Genetic Analyses of Malaysian GEFS+ Patients

AbstractGeneralized epilepsy with febrile seizure plus (GEFS+) is a familial epilepsy syndrome characterized by phenotypic and genetic heterogeneity. Neuronal voltage gated sodium channel α-1 subunit gene, SCN1A is the most clinically relevant and associated with GEFS+. The objective was to study the clinical presentations of GEFS+ and analyze the SCN1A gene associated with Malaysian GEFS+ patients. Blood samples were collected from 30 unrelated GEFS+ patients and genomic DNA was obtained using the Qiagen DNA Blood Mini Kit following the manufacturer’s instructions. The 26 exons of SCN1A genes were analyzed by polymerase chain reaction (PCR) and denaturing high performance liquid chromatography (DHPLC). The aberrant profile peak from DHPLC analysis was confirmed by direct sequencing. The spectrum of phenotypes observed in Malaysian GEFS+ patients included febrile seizure (FS), febrile seizure plus (FS+) and afebrile generalized tonic clonic seizure (AGTCS). Direct sequencing of SCN1A revealed seven sequence variants including one novel SCN1A mutation that was associated with GEFS+. This suggests that mutation of the SCN1A gene is one of the prevalent causes of GEFS+ in Malaysia.