Purpose: Previous linkage studies provided evidence for juvenile myoclonic epilepsy (JME) susceptibility loci at 6p11-12, HLA-6p21.3 region, 15q14, and 5q34. These results indicate locus heterogeneity or interpopulation differences, thus underlining the importance of replication studies. Methods: We describe a replication linkage study of the 6p-q13 region in 18 families ascertained from JME probands of Dutch descent. In the presence of heterogeneity, the definition of the disease status may be crucial, and we therefore used two disease phenotypes: narrow [JME/idiopathic generalized epilepsy (IGE)-"only"] and broad (JME/IGE-plus-fast EEG background activity). Results: We found evidence of linkage at 6p11-12 in multipoint analyses (p < 0.01 in a replication study) for both these disease definitions. Analysis of this region, assuming heterogeneity and autosomal dominant inheritance with a conservative 60% of penetrance, gave a maximum multipoint parametric lod score of 2.07 at D6S1573 for the narrow phenotype and peaked at 2.53 between D6S1623 and D6S1573 for the broad phenotype. The p value for nonparametric linkage reached 0.0013 for the narrow phenotype and 0.0010 for the broad. Significant exclusion (lod score ≤2) was found for the HLA region and for 10 to 30 cM telomeric to HLA. Our results provide evidence for a susceptibility locus for JME/IGE-plus-fast EEG background activity at 6p11-12. Conclusions: Additionally, by using a narrow definition, we were able to confirm previous evidence for a JME-IGE locus at this location.

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doi.org/10.1111/j.0013-9580.2004.36003.x, hdl.handle.net/1765/62922
Department of Clinical Genetics

Pinto, D, de Haan, G.-J, Janssen, G.A.M.A.J, Boezeman, E.H, van Erp, M.G, Westland, B, … Koeleman, B.P.C. (2004). Evidence for Linkage between Juvenile Myoclonic Epilepsy-Related Idiopathic Generalized Epilepsy and 6p11-12 in Dutch Families. Epilepsia, 45(3), 211–217. doi:10.1111/j.0013-9580.2004.36003.x