title: Genetic mapping of a major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q.
abstract: 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.
authors.affiliation: Department of Paediatrics, University College London Medical School, The Rayne Institute, UK.
authors.forename: F V
authors.initials: FV
authors.lastname: Elmslie
authors.forename: M
authors.initials: M
authors.lastname: Rees
authors.forename: M P
authors.initials: MP
authors.lastname: Williamson
authors.forename: M
authors.initials: M
authors.lastname: Kerr
authors.forename: M J
authors.initials: MJ
authors.lastname: Kjeldsen
authors.forename: K A
authors.initials: KA
authors.lastname: Pang
authors.forename: A
authors.initials: A
authors.lastname: Sundqvist
authors.forename: M L
authors.initials: ML
authors.lastname: Friis
authors.forename: D
authors.initials: D
authors.lastname: Chadwick
authors.forename: A
authors.initials: A
authors.lastname: Richens
authors.forename: A
authors.initials: A
authors.lastname: Covanis
authors.forename: M
authors.initials: M
authors.lastname: Santos
authors.forename: A
authors.initials: A
authors.lastname: Arzimanoglou
authors.forename: C P
authors.initials: CP
authors.lastname: Panayiotopoulos
authors.forename: D
authors.initials: D
authors.lastname: Curtis
authors.forename: W P
authors.initials: WP
authors.lastname: Whitehouse
authors.forename: R M
authors.initials: RM
authors.lastname: Gardiner
mesh_terms: D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15; D004831:Epilepsies, Myoclonic / Q000235:genetics*; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D011978:Receptors, Nicotinic / Q000235:genetics
chemical_list: D011978:Receptors, Nicotinic