High prevalence of genetic alterations in early-onset epileptic encephalopathies associated with infantile movement disorders
High prevalence of genetic alterations in early-onset epileptic encephalopathies associated with infantile movement disorders
复制标题
DOI：
10.1016/j.braindev.2015.09.011
复制
发表时间：
2016-03-01
影响因子：
1.7
通讯作者：
Matsumoto, Naomichi
中科院分区：
文献类型：
--
作者：
Kobayashi, Yu;Tohyama, Jun;Matsumoto, Naomichi
目的：最近的研究阐明了早发性癫痫性脑病（EOEE）遗传异常的致病作用。除了癫痫发作外，伴随的特征也被认为为受影响患者的早期和准确的遗传诊断提供了重要线索。在这项研究中，我们调查了与婴儿运动障碍相关的EOEE患者的潜在遗传原因。方法：我们检查了11例EOEE和不自主运动患者（9例为West综合征，2例为非综合征性癫痫性脑病）。所有患者均表现出严重的发育迟缓、认知障碍和不自主运动，如舞蹈病、弹道症、运动障碍或肌阵挛，以及手部刻板印象。我们对10名患者进行了全外显子组测序，而另一名患者进行了候选EOEE基因的高分辨率熔化分析。结果：我们在7例West综合征患者中发现了CDKL5、SCN2A、SETD5、ALG13和TBL1XR1突变，在2例未分类癫痫性脑病患者中发现了SCN1A和GRIN1突变。所有突变均为新生事件。其余两名患者的遗传原因尚未确定。结论：我们在11例EOEE和不自主运动患者中的9例中发现了7个基因的致病性突变。虽然我们的研究结果是初步的，因为患者数量少，但他们仍然表明，特定的伴随表型，如多动运动或手部刻板印象，可能在缩小疾病范围和确定致病遗传异常方面很重要。(C) 2015日本儿童神经病学学会。Elsevier B.V.版权所有。
Objective: Recent studies have elucidated causative roles for genetic abnormalities in early-onset epileptic encephalopathies (EOEE). Accompanying characteristic features, in addition to seizures, have also been suggested to provide important clues for an early and accurate genetic diagnosis of affected patients. In this study, we investigated the underlying genetic causes in patients with EOEE associated with infantile movement disorders.Methods: We examined 11 patients with EOEE and involuntary movements (nine with West syndrome and two with nonsyndromic epileptic encephalopathy). All showed severe developmental delay, cognitive impairment, and involuntary movements such as chorea, ballism, dyskinesia or myoclonus, and hand stereotypies. We performed whole-exome sequencing of 10 patients, while the other patient underwent high-resolution melting analysis of candidate EOEE genes.Results: We identified mutations in CDKL5, SCN2A, SETD5, ALG13, and TBL1XR1 in seven patients with West syndrome, and in SCN1A and GRIN1 in the two patients with unclassified epileptic encephalopathy. All mutations were validated as de novo events. The genetic cause was undetermined in the remaining two patients.Conclusions: We found pathogenic mutations in seven genes, in nine of 11 patients with EOEE and involuntary movements. Although the results of our study are preliminary because of the small number of patients, they nevertheless suggest that specific accompanying phenotypes such as hyperkinetic movements or hand stereotypies could be important in narrowing the disease spectrum and identifying causative genetic abnormalities. (C) 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.