Juvenile myoclonic epilepsy in chromosome 6p12-p11: Locus heterogeneity and recombinations

✍ Scribed by Liu, A. W.; Delgado-Escueta, A. V.; Gee, M. N.; Serratosa, J. M.; Zhang, Q. W.; Alonso, M. E.; Medina, M. T.; Cordova, S.; Zhao, H. Z.; Spellman, J. M.; Donnadieu, F. Rubio; Peek, J. Ramos; Treiman, L. J.; Sparkes, R. S.

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 76 KB
• Volume: 63
• Category: Article
• ISSN: 0148-7299
• DOI: 10.1002/(sici)1096-8628(19960614)63:3<438::aid-ajmg5>3.0.co;2-n

✦ Synopsis

We recently analyzed under homogeneity a large pedigree from Belize with classic juvenile myoclonic epilepsy (JME). After a genome wide search with 146 microsatellites, we obtained significant linkage between chromosome 6p markers, D6S257 and D6S272, and both convulsive and EEG traits of JME. Recombinations in two affected members defined a 40 cM JME region flanked by D6S313 and D6S258. In the present communication, we explored if the same chromosome 6pll microsatellites also have a role in JME mixed with pyknoleptic absences. We allowed for heterogeneity during linkage analyses. We tested for heterogeneity by the admixture test and looked for more recombinations. D6S272, D6S466, D6S294, and D6S257 were significantly linked (Z,,, > 3.5) to the clinical and EEG traits of 22 families, assuming autosomal dominant inheritance with 70% penetrance.

Pairwise Z, , , were 4.230 for D6S294 (Om=, at 0.133) and 4.442 for D6S466 (Om=, at 0.111). Admixture test (H, vs. HI) was significant (P = 0.0234 for D6S294 and 0.0128 for D65272) supporting the hypotheses of linkage with heterogeneity. Estimated proportion of linked families, a, was 0.50 (95% confidence interval 0.05-0.99) for D6S294 and D6S272. Multipoint analyses and recombinations in three new families narrowed the JME locus to a 7 cM interval flanked by D6S272 and D6S257. o 1996 Wiley-Liss, Inc.