Abstracts

Juvenile myoclonic epilepsy (JME) is a common epilepsy syndrome with genetic heterogeneity. Four mutation-harbouring genes for JME, CACNB4 on chromosome 2q22-23, GABRA1 on chromosome 5q34, CLCN2 on chromosome 3q26, and EFHC1 on 6p12, have been identified. In addition, association study identified three susceptibility genes to JME in JME loci identified by linkage analysis. They are BRD2 in 6p21.3, connexin 36 gene in 15q14 and ME2 in 18q21. This study presents the results of association study between JME and the coding SNPs of EFHC1 in 6p12. We genotyped four SNPs, rs3804505, rs3804506, rs1266787 and 1855 A[gt]C in the coding region of EFHC1 in 130 unrelated JME probands, 108 nuclear JME families from Spanish Amerind population and 600 ethnic matched normal controls. We performed case-control association analysis between JME probands and normal controls and transmission disequilibrium test (TDT) for rs3804505, rs3804506 in the 108 nuclear JME families with the TDT and FBAT program. In case-control analysis, none of the genotype counts and the allele frequency of the four coding SNPs in JME between 130 JME probands and 600 normal controls reached to statistical significance (P[lt]0.05). In TDT, the genotype counts from both SNPs rs3804506 and 3804505 for father, mother, affected children and unaffected children in 108 nuclear families did not deviate from Hardy-Weinberg equilibrium under the hypothesis of no linkage and no association. We got the same negative results testing under linkage and no association with FBAT program. The present study suggested that it is unlikely that the four coding SNPs, rs3804505, rs3804506, rs1266787 and 1855 A[gt]C in EFHC1 play an important role in the genetic predisposition to JME. (Supported by R01 NS042376.)