Abstracts

RATIONALE: CAE accounts for 5-15% of all childhood epilepsies. In 1998, we mapped the locus for CAE that persists with grand mal in chromosome 8q24 using families from India, USA, Argentina, Saudi Arabia and Spain. In 1999, Feucht et al., using Transmission Disequilibrium Test, showed significant association between Austrian CAE families and GABRB3. Our objective is to perform linkage analyses between three subsyndromes of CAE (remitting CAE, persisting CAE with and without grand mal, and CAE with and without eyelid myoclonia evolving to JME) and GABRB3 and surrounding microsatellites in chromosome 15q11.2-12. METHODS: We ascertained 21 families from California (USA), Mexico, Spain, Canada and Hong Kong (China) through a proband with pyknoleptic CAE. We genotyped with D15S122, GABRB3, 69CA, 155CA1, 155CA2, 85CA, A55CA1, GABRA5 and D15S165 using standard PCR protocols (Weber & May, 1989). Two-point linkage analysis used LINKAGE version 5.21. RESULTS: We obtained exclusionary lod scores at ?m=f=0: -2.2 for one medium-sized family (6 affected) and -6.3 for one large family (13 affected) with CAE with eyelid myoclonia, -7.3 for six families (16 affected) with persisting CAE only or CAE persisting with grand mal, and -17.2 for seven families (42 affected) with CAE evolving to JME. However, the pooled lod score was positive (2.11 at ?m=f=0) for GABRB3 in eight families (17 affected) with remitting CAE. CONCLUSIONS: The subsyndromes of persisting CAE with grand mal, eyelid myoclonia and/or JME are not linked to chromosome 15q11.2-12. In remitting CAE, the pooled lod score suggests linkage to GABRB3, although the lod score has not yet reached significance.