Elmslie FV, Rees M, Williamson MP, Kerr M, Kjeldsen MJ, Pang KA, Sundqvist A, Friis ML,
Chadwick D, Richens A, Covanis A, Santos M, Arzimanoglou A, Panayiotopoulos CP, Curtis D,
Whitehouse WP, Gardiner RM.
Genetic mapping of a major susceptibility locus for juvenile
myoclonic epilepsy on chromosome 15q. Hum Mol Genet 1997 6: 1329-34.
The epilepsies are a group of disorders characterised by recurrent seizures caused by episodes of abnormal
neuronal hyperexcitability involving the brain. Up to 60 million people are affected worldwide and genetic
factors may contribute to the aetiology in up to 40% of patients. The most common human genetic epilepsies
display a complex pattern of inheritance. These are categorised as idiopathic in the absence of detectable
structural or metabolic abnormalities. Juvenile myoclonic epilepsy (JME) is a distinctive and common variety of
familial idiopathic generalised epilepsy (IGE) with a prevalence of 0.5-1.0 per 1000 and a ratio of sibling risk
to population prevalence (lambda(s)) of 42. The molecular genetic basis of these familial idiopathic epilepsies is
entirely unknown, but a mutation in the gene CHRNA4, encoding the alpha4 subunit of the neuronal nicotinic
acetylcholine receptor (nAChR), was recently identified in a rare Mendelian variety of idiopathic epilepsy.
Chromosomal regions harbouring genes for nAChR subunits were therefore tested for linkage to the JME trait
in 34 pedigrees. Significant evidence for linkage with heterogeneity was found to polymorphic loci
encompassing the region in which the gene encoding the alpha7 subunit of nAChR (CHRNA7) maps on
chromosome 15q14 (HLOD = 4.4 at alpha = 0.65; Z(all) = 2.94, P = 0.0005). This major locus contributes
to genetic susceptibility to JME in a majority of the families studied.
Dave Curtis publications