Genetic mapping of a major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q
Genetic mapping of a major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q
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DOI：
10.1093/hmg/6.8.1329
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发表时间：
1997-08-01
影响因子：
3.5
通讯作者：
Gardiner, RM
中科院分区：
文献类型：
--
作者：
Elmslie, FV;Rees, M;Gardiner, RM
癫痫是一组以涉及大脑的异常神经元过度兴奋发作引起的反复发作为特征的疾病，全世界有多达 6000 万人受到影响，遗传因素可能导致高达 40% 患者的病因。最常见的人类遗传性癫痫表现出复杂的遗传模式。在没有可检测到的结构或代谢异常的情况下，这些疾病被归类为特发性癫痫。青少年肌阵挛性癫痫 (JME) 是一种独特而常见的家族性特发性全身性癫痫 (IGE)，患病率为每 1000 人 0.5-1.0 例，兄弟姐妹风险与人群患病率 (lambda(s)) 之比为 42。 这些家族性特发性癫痫的遗传基础完全未知，但最近在一种罕见的孟德尔特发性癫痫中发现了编码神经元烟碱乙酰胆碱受体（nAChR）的α4亚基的基因CHRNA4的突变，因此对含有nAChR亚基基因的染色体区域进行了连锁测试 34个谱系中的JME特征。发现了与异质性连锁的重要证据，该基因座包含编码 nAChR (CHRNA7) α 7 亚基的基因映射在染色体 15q14 上的区域（HLOD = 4.4，α = 0.65；Z(all) = 2.94，P = 0.0005），该主要位点导致大多数家族对 JME 的遗传易感性 研究过。
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 alpha 4 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 alpha 7 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.