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Genetic mapping of a major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q

1997; Oxford University Press; Volume: 6; Issue: 8 Linguagem: Inglês

10.1093/hmg/6.8.1329

1460-2083

Frances Elmslie, Michelle Rees, Magali Williamson, Michael Kerr, Marianne Juel Kjeldsen, Kiang An Pang, Anders Sundqvist, M. L. Friis, David Chadwick, A. Richens, Athanasios Covanis, Mauro Santos, Alexis Arzimanoglou, C. P. Panayiotopoulos, David Curtis, William Whitehouse, R M Gardiner,

Neuroscience and Neuropharmacology Research

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 (λs) of 42. The molecular genetic basis of these familial idiopathic epilepsies is entirely unknown, but a mutation in the gene CHRNA4, encoding the a4 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 α7 subunit of nAChR (CHRNA7) maps on chromosome 15q14 (HLOD = 4.4 at α = 0.65; Zall = 2.94, P = 0.0005). This major locus contributes to genetic susceptibility to JME in a majority of the families studied.