Phenotypic spectrum of GNAO1 variants: epileptic encephalopathy to involuntary movements with severe developmental delay
Phenotypic spectrum of GNAO1 variants: epileptic encephalopathy to involuntary movements with severe developmental delay
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DOI：
10.1038/ejhg.2015.92
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发表时间：
2016-01-01
影响因子：
5.2
通讯作者：
Matsumoto, Naomichi
中科院分区：
文献类型：
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作者：
Saitsu, Hirotomo;Fukai, Ryoko;Matsumoto, Naomichi
在四名患者中发现了从头GNAO 1变体，包括三名Ohtahara综合征患者和一名儿童癫痫患者。此外，两名患者表现出不自主运动，这表明GNAO 1变异体可导致各种神经学表型。在这里，我们报告了另外四名患者的从头错义GNAO 1变异，其中一个是相同的，以前报道的。通过结构评估，预测所有三种新变体都会损害Gao功能。两名患者表现为早发性癫痫性脑病，在其临床过程中表现为迁移性或多灶性部分性癫痫发作，但其余两名患者表现为无或少数癫痫发作。所有四名患者均表现出严重的智力残疾、运动发育迟缓和不自主运动。进行性脑萎缩和胼胝体变薄是常见的脑影像学特征。我们的研究表明，GNAO 1变体可导致不自主运动和严重的发育迟缓，伴/不伴癫痫发作，包括各种类型的早发性癫痫性脑病。
De novo GNAO1 variants have been found in four patients including three patients with Ohtahara syndrome and one patient with childhood epilepsy. In addition, two patients showed involuntary movements, suggesting that GNAO1 variants can cause various neurological phenotypes. Here we report an additional four patients with de novo missense GNAO1 variants, one of which was identical to that of the previously reported. All the three novel variants were predicted to impair Gao function by structural evaluation. Two patients showed early-onset epileptic encephalopathy, presenting with migrating or multifocal partial seizures in their clinical course, but the remaining two patients showed no or a few seizures. All the four patients showed severe intellectual disability, motor developmental delay, and involuntary movements. Progressive cerebral atrophy and thin corpus callosum were common features in brain images. Our study demonstrated that GNAO1 variants can cause involuntary movements and severe developmental delay with/without seizures, including various types of early-onset epileptic encephalopathy.