Abstracts

Because absence seizures occur in Angelman syndrome (Minassian et al, 1998), because GABRB3 genetically associate with CAE ( Feucht et.al., 1999) and because of a summed LOD of 2.5 (q=0, 50% penetrance) at GABRB3 and 85CA primer loci in remitting CAE (Tanaka et al,2000), we studied a one Kb region that includes the core promoter region and Exon1a of GABRB3 on chromosome 15q11.2-12 in CAE syndrome. We studied 41 families (three Canadian, two Spanish, three European American, 26 Mexican, 7 Honduranean) with remitting or persisting CAE with/without eyelid myoclonias, or CAE with GM. We designed primers which overlapped about one Kb telomeric region from Exon1a and Exon1a. We directly sequenced these PCR products of probands. For 440 Mexican and Honduranean controls, we screened for mutations by denaturing high-performance liquid chromatography. In non-coding region, we did not find any novel single nucleotide polymorphisms (SNPs). We observed missense mutation (Ser15Phe) in a Honduranean proband and (Pro11Ser) in a Hermosillo (Mexico) proband and a Mexico city proband.In 440 Mexican and Honduranean controls we did not find any of the above missense mutations. We are now studying these three multigeneration families. Missense mutations were observed in 3 probands with CAE. GABRB3 has an alternative Exon1 namely Exon1a which encodes an alternative signal peptide whose expression level is rich in the developing neonatal brain and decreases in the adult brain (Kirkness and Fraser,1993). Missense mutation in Exon1a which disappears with age may explain why the CAE phenotype can remit. Further studies should test this notion.