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

Abstract

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 6p11 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 (Zmax > 3.5) to the clinical and EEG traits of 22 families, assuming autosomal dominant inheritance with 70% penetrance. Pairwise Zmax were 4.230 for D6S294 (θm = f at 0.133) and 4.442 for D6S466 (θm = f at 0.111). Admixture test (H2 vs. H1) was significant (P = 0.0234 for D6S294 and 0.0128 for D6S272) supporting the hypotheses of linkage with heterogeneity. Estimated proportion of linked families, α, 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. © 1996 Wiley‐Liss, Inc.

Headache in juvenile myoclonic epilepsy

“…Clarke et al [27] found a migraine prevalence of 15% in children with the homogenous epilepsy subtype rolandic epilepsy in contrast to 7% in non-epilepsy probands. Since JME has a strong genetic background (positive family history of seizures in at least 40% [10]), headache and especially MA in JME, but maybe not in the general population, might also have such a strong genetic background. We suggest that our findings support using the relationship of JME and MA to further study the genetics of both disease entities.…”

“…The main seizure types are myoclonic jerks, generalized tonic-clonic seizures and, less frequently, absences [9]. The syndrome has a strong genetic background with at least 40% of patients presenting a positive family history [10]. Intensive genetic studies could identify genes associated with JME coding for various ion channels, but also acetylcholine receptors, lysosomal membranes, and for the regulation of apoptosis (review in [11]).…”

Molecular Cloning and Functional Expression of KCNQ5, a Potassium Channel Subunit That May Contribute to Neuronal M-current Diversity

“…By fluorescence in situ hybridization analysis, we mapped the KCNQ5 gene to chromosome 6q14. There are two known loci on chromosome 6 linked to epileptic diseases, a cloned gene at 6q24 (EPM2A), which is defective in progressive myoclonic epilepsy type 2 (40,41), and an unknown gene mapped to 6p12-p11, which is responsible for juvenile myoclonic epilepsy (JME) (42). Although our mapping results probably exclude involvement of KCNQ5 in JME, the identification of KCNQ5 makes it now possible to investigate possible associations with other forms of epilepsy or inherited neurological diseases.…”

Juvenile Myoclonic Epilepsy and Migraine: Study of Comorbidity and Clinical Co-Occurrence.

“…Since both JME and migraine are highly linked to genetic and hereditary basis, in our study positive family history of migraine was found to a higher incidence in JME cases with migraine 60 % compared to only 25% positive family history of migraine JME cases with migraine which supports a strong genetic background (25).…”