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- CEPH, Centre d’Etude du Polymorphisme Humain
- ESE, exonic splicing enhancer
- HW, Hardy-Weinberg
- ILAE, International League Against Epilepsy
- JME, juvenile myoclonic epilepsy
- LD, linkage disequilibrium
- RS, randomly selected
- SNP, single nucleotide polymorphism
Epilepsy is one of the most common and serious neurological disorders, with up to 60 million people affected worldwide.1 Juvenile myoclonic epilepsy (JME) is a common familial form that accounts for 5–10% of all epilepsy cases.2 This form belongs to the idiopathic epilepsy group, due to the absence of detectable structural or metabolic abnormalities. Clinically, JME is mainly characterised by isolated myoclonic jerks on awakening that usually begin during adolescence. It is also highly drug-dependent, since a 90% recurrence is reported after interruption of pharmacological treatment.3
Studies on the incidence of epilepsy in relatives of probands with JME, as well as on twins, have provided strong evidence for a genetic contribution.4,5 Autosomal dominant, autosomal recessive, two locus, monogenic, and polygenic models of inheritance have been suggested.6 So far, three genes that are mutated in different forms of JME have been identified, namely CACNB4,7GABRA1,8 and CLCN2.9 In addition, two different susceptibility loci have been identified by linkage analysis. The first locus, termed EJM1 (OMIM 254770), is on the human leukocyte antigen region of chromosome 6p.10 Although no trait-causing mutation has yet been identified at this locus, association with a haplotype of the BRD2 gene has been recently reported.11 The second locus, termed EJM2 (OMIM 604827), is in the region of chromosome 15q that contains the gene coding for the α7-nicotinic acetylcholine receptor subunit. Genetic mapping of the EJM2 locus defined a 15.1 cM candidate region on chromosome 15q14, flanked by the D15S165 and D15S971 loci.6 Interestingly, this region includes the CX36 gene, which codes for the first connexin identified in neurons.12
Connexins are integral membrane proteins, encoded by a family of at least 20 genes in humans, which form the subunits of gap junction …
↵* These authors contributed equally to this work.
CM is supported by the Fondation Romande pour la Recherche sur le Diabete and the Swiss Academy of Medical Sciences (Theodore Ott-Fund 07/01). The work of the Meda team is supported by grants from the Swiss National Foundation (3100-067788.02), the Juvenile Diabetes Research Foundation International (1-2001-622 and 5-2004-255), the European Union (QLRT-2001-01777), and the National Institute of Health (DK 63443-01). The work of the Antonarakis team is supported by grants from the Swiss National Foundation (31.57149.99), the European Union (QLG1-2002-00816) and the National Center for Competence in Research “Frontiers in Genetics”. The work of the Gardiner team is supported by the UK Medical Research Council.
Conflict of interest: none declared.