A de novo GABRA2 missense mutation in severe early-onset epileptic encephalopathy with a choreiform movement disorder
A de novo GABRA2 missense mutation in severe early-onset epileptic encephalopathy with a choreiform movement disorder
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DOI：
10.1016/j.ejpn.2017.12.017
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发表时间：
2018-05-01
影响因子：
3.1
通讯作者：
Basel-Salmon, Lina
中科院分区：
文献类型：
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作者：
Orenstein, Naama;Goldberg-Stern, Hadassa;Basel-Salmon, Lina
背景：早发性癫痫性脑病（EOEE）是一种严重的惊厥性疾病，发育预后不良。尽管它与许多基因突变有关，但仍有很大一部分患者未被诊断的事实表明，EOEE 还有许多未知的遗传原因。实现基因诊断对于了解该疾病的生物学基础及其对治疗和计划生育的影响非常重要。方法：对一个德系犹太人血统的家庭进行全外显子组测序，该家庭的一名男婴被诊断患有 EOEE。没有类似神经系统疾病的家族史。除了惊厥障碍外，患者还患有肌张力严重减退、新生儿体温过低、舞蹈样运动和视力障碍。 结果：在 GABRA2 的保守域中发现了新的杂合错义突变 c.1003A > C，p.Asn335His。 GABRA2 编码 GABA(A) 受体的 α2 亚基。结论：根据之前关于编码 GABA(A) 受体不同亚基（GABRB1、GABRA1、GABRG2、GABRB3）的基因的新生突变与常染色体显性癫痫病相关的报道，我们得出结论， GABRA2 可能会导致常染色体显性遗传 EOEE，并伴有运动障碍和视力障碍。 (C) 2017 年欧洲小儿神经病学协会。由爱思唯尔有限公司出版。保留所有权利。
Background: Early-onset epileptic encephalopathy (EOEE) is a severe convulsive disorder with a poor developmental prognosis. Although it has been associated with mutations in a number of genes, the fact that there is a large proportion of patients who remain undiagnosed suggests that there are many more still-unknown genetic causes of EOEE. Achieving a genetic diagnosis is important for understanding the biological basis of the disease, with its implications for treatment and family planning.Methods: Whole-exome sequencing was performed in a family of Ashkenazi Jewish origin in which a male infant was diagnosed with EOEE. There was no family history of a similar neurologic disease. The patient had extreme hypotonia, neonatal hypothermia, choreiform movements, and vision impairment in addition to the convulsive disorder.Results: A de novo heterozygous missense mutation, c.1003A > C, p.Asn335His, was identified in a conserved domain of GABRA2. GABRA2 encodes the alpha 2 subunit of the GABA(A) receptor.Conclusions: In the context of previous reports of an association of de novo mutations in genes encoding different subunits of the GABA(A) receptor (GABRB1, GABRA1, GABRG2, GABRB3) with autosomal dominant epileptic disorders, we conclude that a de novo mutation in GABRA2 is likely to cause autosomal dominant EOEE accompanied by a movement disorder and vision impairment. (C) 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.