Genetic mapping of a major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q |
| |
Authors: | 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 |
| |
Institution: | Department of Paediatrics, University College London Medical School, The Rayne Institute, UK. |
| |
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.
|
| |
Keywords: | |
本文献已被 Oxford 等数据库收录! |
|