GRIN1 mutations cause encephalopathy with infantile-onset epilepsy, and hyperkinetic and stereotyped movement disorders
GRIN1 mutations cause encephalopathy with infantile-onset epilepsy, and hyperkinetic and stereotyped movement disorders
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DOI：
10.1111/epi.12987
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发表时间：
2015-06-01
期刊：
影响因子：
5.6
通讯作者：
Matsumoto, Naomichi
中科院分区：
文献类型：
--
作者：
Ohba, Chihiro;Shiina, Masaaki;Matsumoto, Naomichi
目的近年来，在非综合征性智能障碍和癫痫脑病患者中发现了GRIN1基因的从头突变。对遗传未解决的癫痫脑病患者进行全外显子测序(WES)分析，发现4例患者存在GRIN1突变，使我们能够研究GRIN1突变的表型谱。方法在1例患者中检测到88例发病年龄为A的未分类早发性癫痫脑病(EOEE)患者的突变等位基因频率为16%(在血白细胞DNA中)。三个突变位于跨膜区(3/4，75%)，一个位于跨膜螺旋1附近的细胞外环。所有这些突变都被预测为损害NMDA受体的功能。显著的临床特征包括婴儿不自主运动、癫痫发作和手的刻板印象，这表明GRIN1突变导致脑病，导致癫痫和运动障碍。
ObjectiveRecently, de novo mutations in GRIN1 have been identified in patients with nonsyndromic intellectual disability and epileptic encephalopathy. Whole exome sequencing (WES) analysis of patients with genetically unsolved epileptic encephalopathies identified four patients with GRIN1 mutations, allowing us to investigate the phenotypic spectrum of GRIN1 mutations.MethodsEighty-eight patients with unclassified early onset epileptic encephalopathies (EOEEs) with an age of onset A) with a mutant allele frequency of 16% (in DNA of blood leukocytes) was detected in one patient. Three mutations were located in the transmembrane domain (3/4, 75%), and one in the extracellular loop near transmembrane helix 1. All the mutations were predicted to impair the function of the NMDA receptor.SignificanceClinical features of de novo GRIN1 mutations include infantile involuntary movements, seizures, and hand stereotypies, suggesting that GRIN1 mutations cause encephalopathy resulting in seizures and movement disorders.