Genome scan of idiopathic generalized epilepsy: Evidence for major susceptibility gene and modifying genes influencing the seizure type
Genome scan of idiopathic generalized epilepsy: Evidence for major susceptibility gene and modifying genes influencing the seizure type
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DOI：
10.1002/ana.69
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发表时间：
2001-03-01
影响因子：
11.2
通讯作者：
Greenberg, DA
中科院分区：
文献类型：
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作者：
Durner, M;Keddache, MA;Greenberg, DA
特发性全身性癫痫(IGE)是一种常见的复杂疾病，几乎完全由遗传因素引起，但具有不同的表型。临床上，IgE可分为不同证型。不同的证据表明，几个相互作用的基因参与了IgE的病因学。我们对91个家系进行了基因组扫描，这些家系都是青春期发病的IGE先证者。IGES包括青少年肌阵挛癫痫(JME)、青少年失神癫痫(JAE)和癫痫伴全身强直阵挛发作(EGTCS)。我们的连锁结果支持免疫球蛋白E的寡基因模型，有强有力的证据表明18号染色体上有一个大多数IGES共同的基因座(IoD分数4.4/5.2多点/两点)和其他可能影响不同IGE特异性癫痫表型的基因座：6号染色体上先前发现的JME基因座(Lod分数2.5/4.2)，8号染色体上影响非JME形式的IGE的基因座(IoD分数3.8/2.5)，以及更暂定的5号染色体上新发现的两个失神癫痫基因座(IoD分数3.8/2.8和3.4/1.9)。我们的数据还表明，不同形式的免疫球蛋白E的基因分类可能会跨越这些亚型的临床分类。我们假设，这些基因座的不同组合的相互作用产生了在免疫球蛋白E家族中看到的相关的异质性表型。
Idiopathic generalized epilepsy (IGE) is a common, complex disease with an almost exclusively genetic etiology but with variable phenotypes. Clinically, IGE can be divided into different syndromes. Varying lines of evidence point to the involvement of several interacting genes in the etiology of IGE. We performed a genome scan in 91 families ascertained through a proband with adolescent-onset IGE. The IGEs included juvenile myoclonic epilepsy (JME), juvenile absence epilepsy (JAE), and epilepsy with generalized tonic clonic seizures (EGTCS). Our linkage results support an oligogenic model for IGE, with strong evidence for a locus common to most IGEs on chromosome 18 (Iod score 4.4/5.2 multipoint/two-point) and other loci that may influence specific seizure phenotypes for different IGEs: a previously identified locus on chromosome 6 for JME (lod score 2.5/4.2), a locus on chromosome 8 influencing non-JME forms of IGE (Iod score 3.8/2.5), and, more tentatively, two newly discovered loci for absence seizures on chromosome 5 (Iod scores 3.8/2.8 and 3.4/1.9). Our data also suggest that the genetic classification of different forms of IGE is likely to cut across the clinical classification of these subforms of IGE. We hypothesize that interactions of different combinations of these loci produce the related heterogeneous phenotypes seen in IGE families.