SEQUENCE VARIANTS OF GABRB3, GABRA5 AND GABRB3 ON CHROMOSOME 15Q 11.2-12 IN REMITTING CHILDHOOD ABSENCE EPILEPSY
Abstract number :
1.200
Submission category :
Year :
2003
Submission ID :
4044
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
Miyabi Tanaka, Ignacio P. Castroviejo, Jesus Machado-Salas, Gregorio S. Pineda, Berge Minnasian, Marco T. Medina, Chung Y. Fong, Julia Bailey, Dongsheng Bai, Richard W. Olsen, Antonio V. Delgado-Escueta Comprehensive Epilepsy Center, University of Califor
Because possible genetic linkage has been observed between A55CA1 (HLOD 1.8 with theta=0.37, AR model and NPL-2.5 with p=0.0004) (Robinson et al. [italic]Epilepsia[/italic] 2002; 43 supp.7:277) and GABRB3, 85CA, GABRA5 (all with LOD 2.5 with theta =0)(Tanaka et al. [italic]Epilepsia[/italic] 2000; 41 supp.7:250) and remitting Childhood Absence Epilepsy (r-CAE) in two separate and independent cohorts from Europe/London and Los Angeles/Mexico, we investigated the possible association of sequence variants in GABRB3, GABRA5 and GABRG3 on chromosome 15q 11.2-12 and r-CAE probands.
We studied r-CAE probands of 10 families (3 Canadian, 2 Spanish, 1 European American, 4 European/Amerind) which had originally contributed to a summed LOD of 2.5 (theta=0). Each primer was designed to contain the full length of each exon. For GABRB3 and GABRA5, we extended the region to about 200 bp forward from exon 1a. All r-CAE probands were initially screened with controls by denaturing high performance liquid chromatography. Suspected variations were then sequenced.
Six single nucleotide polymorphisms (SNPs) were found. C30G (NCBI L04311) 10bp telomeric from exon 1a of GABRB3 and C170T (NCBI L04311) in exon 1a of GABRB3 are present in 6 of 10 r-CAE probands, in 10 of 41 European controls and 32 of 39 European/Amerinds. In GABRA5, C231T in intron 5 (NCBI AF228447) and C268T, (NCBI AF228447) in exon 6 are each present in 1 of 6 r-CAE Caucasian probands while in 0/39 Caucasian controls. A1473G (NCBI NM_000810) in exon 11 of GABRA5 and T413C, (NCBI AF269142) in exon8 of GABRG3 did not show any differences with controls.
Although our results are preliminary, the observed differences in SNP C231T in intron 5 and C268T in exon 6 of GABRA5 between r-CAE probands and controls are promising. Further recruitment of 100 new CAE probands are in progress and results of their SNP screens will be presented.