A longer polyalanine expansion mutation in the ARX gene causes early infantile epileptic encephalopathy with suppression-burst pattern (Ohtahara syndrome)
A longer polyalanine expansion mutation in the ARX gene causes early infantile epileptic encephalopathy with suppression-burst pattern (Ohtahara syndrome)
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DOI：
10.1086/518903
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发表时间：
2007-08-01
影响因子：
9.8
通讯作者：
Hayasaka, Kiyoshi
中科院分区：
文献类型：
--
作者：
Kato, Mitsuhiro;Saitoh, Shinji;Hayasaka, Kiyoshi
早期婴儿癫痫发作模式脑病(EIEE)是最严重和最早的癫痫类型之一，常演变为West综合征，但其发病机制尚不清楚。ARX是胎儿大脑中间神经元发育的关键基因，APX的聚丙氨酸扩张性突变会导致男性智力低下和癫痫发作，包括West综合征。我们对ARX突变进行了筛查，发现在三例无关的男性ELEE患者中，有两例在外显子2 298_330dupGCGGCA(GCG)(9)上存在半合子重复，从头开始，33个碱基重复。这种突变被认为将ARX蛋白的第一个聚丙氨酸链中最初的16个丙氨酸残基扩大到27个丙氨酸残基(A110_A111 Ins AAAAAAAAAA)。虽然Elee主要与大脑畸形有关，但ARX是第一个被发现与特发性EIEE有关的基因。我们观察到Elee的聚丙氨酸束扩张时间比West综合征更长，这与Elee的发病更早、表型比West综合征更严重的发现是一致的。
Early infantile epileptic encephalopathy with suppression-burst pattern (EIEE) is one of the most severe and earliest forms of epilepsx,, often evolving into West syndrome; however, the pathogenesis of EIEE remains unclear. ARX is a crucial,gene for the development of interneurons in the fetal brain, and a polyalanine expansion mutation of APX causes mental retardation and seizures, including those of West syndrome, in males. We screened the ARX mutation and found a hemizygous, de novo, 33-bp duplication in exon 2, 298_330dupGCGGCA(GCG)(9), in two of three unrelated male patients with ElEE. This mutation is thought to expand the original 16 alanine residues to 27 alanine residues (A110_A111 insAAAAAAAAAAA) in the first polyalanine tract of the ARX protein. Although ElEE is mainly associated with brain malformations, ARX is the first gene found to be responsible for idiopathic EIEE. Our observation that ElEE had a longer expansion of the polyalanine tract than is seen in West syndrome is consistent with the findings of earlier onset and more-severe phenotypes in ElEE than in West syndrome.