FP38-WE-02 Genetic study of juvenile myoclonic epilepsy (JME) patients and their family members in a university hospital in North India

Abstract

Background and Objectives: Among the 40-100 million persons with epilepsy worldwide, approximately 50% have generalized epilepsies. Juvenile myoclonic epilepsy (JME) is a common epileptic syndrome and has been classified as idiopathic generalized epilepsy by the International League Against Epilepsy. JME constitutes 10-30% among all cases of epilepsy. The syndrome is characterized by myoclonic jerks, generalized tonic clonic seizures in 80-97% and absence seizures in 12-54% of patients. Age of onset is between 8-20 years with peak age at 15 years. Inheritance in JME is thought to be autosomal dominant with incomplete penetrance. Previous linkage studies on larger JME families have identified 6 different chromosomal loci being involved: 6p12-11, 6p21.3, 15q14, 6q24, 2q22-2q23, and 5q34. Of all the loci identified, only 5q34 lead to identification of a mutation in the GABRA1 gene in a single larger JME family from Quebec, Canada. Candidate gene analyses in multiplex families identified CLCN2 gene as one of the major genes involved in JME. CLCN2 is the first known gene in which both mutations and a common sequence variant confer a range of varying susceptibility effects to genetically complex epilepsies. Such genes are thought to function as genetic “risk factors” but on their own they may not cause epilepsy. These include KCNQ3, BRD2, LGI4, GABRG2 and CACNB4. The objective of this study was to study the genetic association analysis for sequence polymorphisms in the BRD2, LGI4 and GABRG2 genes and the clinical, EEG characteristics in JME probands and their family members.