USING FUNCTIONAL CANDIDATE GENE STRATEGY TO STUDY CHILDHOOD ABSENCE EPILEPSY GENE

Objectives: Childhood absence epilepsy (CAE) is an idiopathic generalized nonconvulsive epilepsy with a complex genetic mode. CAE gene has not been determined. The underlying mechanisms of CAE are considered to be involving thalamocorticalcircuitry. We used association analysis and functional candidate gene strategy to study CAE gene.

Methods: CAE cases (Han ethnicity) were recruited from several hospitals in Beijing with strict inclusion criteria, and informed consent. Normal adults with matched gender from North China as controls. Genomic DNA was extracted from 118 CAE family trios, and PCR amplification of exons and nearby introns, The exon and exon-intron boundary areas of 7 GABA-A receptor subunits, 2 GABA-B receptor subunits, and T-type Calcium channel gene CACNA1G, CACNA1H, and CACNA1I were directly sequenced to identify SNPs and mutations. Then further conduct association studies (case-control, TdT) in both CAE and control groups.

Results: 68 variations have been detected in CACNA1H gene. And among the variations identified, 12 were missense mutations and only found in 14 of the 118 cases in a heterozygous state, but not in any of 230 unrelated controls. The identified missense mutations occurred in the highly conserved residues of the T-type calcium channel gene. In this study, GABA-A, GABA-B receptors and CACNA1G, CACNA1I genes were not associated with CAE.

Conclusion: CACNA1H might be an important susceptibility gene involved in the pathogenesis of CAE. Functional studies of the mutant CACNA1H gene are during working.

(Supported by grants from BNSF 7001003, PUHDGRCF 2000-A-8, BMCSTHO 10210230119)

Keywords: Childhood absence epilepsy T-type Calcium Channel gene CACNALH