JUVENILE MYOCLONIC EPILEPSY IN CHROMOSOME 6P12-P11 - LOCUS HETEROGENEITY AND RECOMBINATIONS

We recently analyzed under homogeneity a large pedigree from Belize wi th classic juvenile myoclonic epilepsy (JME). After st genome wide sea rch with 146 microsatellites, we obtained significant linkage between chromosome 6p markers, D6S2B7 and D6S272, and both convulsive and EEG traits of JME, Recombinations in two affected members defined a 40 cM JME region flanked by D6S313 slid D6S258. In the present communication , we explored if the same chromosome 6p11 microsatellites also have a role in JME mixed with pyknoleptic absences, We allowed for heterogene ity during linkage analyses. We tested for heterogeneity by the admixt ure test and looked for more recombinations. D6S272, D6S466, D6S294, a nd D65257 were significantly linked (Z(max) > 3.5) to the clinical and EEG traits of 22 families, assuming autosomal dominant inheritance wi th 70% penetrance, Pairwise Z(max) were 4.230 for D6S294 (theta(m=f) a t 0.133) and 4.442 for D6S466 (theta(m=f) at 0.111). Admixture test (H -2 vs. H-1) was significant (P = 0.0234 for D6S294 and 0.0128 for D6S2 72) supporting the hypotheses of linkage with heterogeneity, Estimated proportion of linked families, alpha, was 0.50 (95% confidence interv al 0.05-0.99) for D6S294 and D6S272. Multipoint analyses and recombina tions in three new families narrowed the JME locus to a 7 cM interval flanked by D6S272 and D6S257. (C) 1996 Wiley-Liss, Inc.