Novel TBC1D24 Mutations in a Case of Nonconvulsive Status Epilepticus
Novel TBC1D24 Mutations in a Case of Nonconvulsive Status Epilepticus
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DOI：
10.3389/fneur.2018.00623
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发表时间：
2018-07-31
影响因子：
3.4
通讯作者：
Fan, Yuhua
中科院分区：
文献类型：
--
作者：
Li, Jingjing;Liu, Ruihong;Fan, Yuhua
目的：非惊厥性癫痫持续状态（NCSE）是TBC1D24突变患者的一种罕见临床表现。此外，NCSE还没有被报道为一个综合征连同小脑性共济失调和眼肌麻痹。方法：我们在此报告的临床和遗传特征的一个四岁的患者NCSE，小脑性共济失调，眼肌麻痹所造成的迄今不明TBC1D24突变。我们对患者及其父母进行了24小时视频脑电图（EEG）、磁共振成像和基因测序以确定诊断。1416_1437del（p.Ser473Argfs*43）突变，以及先前鉴定的c. TBC1D24中1499C>T（p.Ala500Val）突变，通过使用靶向下一代测序。新的突变（遗传自母亲）是第一个报告的缺失突变超过20 bp的TBC1D24。报告了1例德国婴儿肌阵挛患者从父亲遗传的p.Ala500Val突变，其EEG和神经影像学结果均正常。结论：新发现的TBC1D24突变及其引起的复杂临床表现提示NCSE伴共济失调患者应引起重视。我们进一步建议对这些患者进行基因检测，以避免这种突变的遗传。
Objective: Nonconvulsive status epilepticus (NCSE) is an uncommon clinical manifestation in patients with TBC1D24 mutations. In addition, NCSE has not been reported as a syndrome together with cerebellar ataxia and ophthalmoplegia.Methods: We herein report the clinical and genetic features of a four-year-old patient with NCSE, cerebellar ataxia, and ophthalmoplegia caused by hitherto unidentified TBC1D24 mutations. We performed 24-h video electroencephalogram (EEG), magnetic resonance imaging, and gene sequencing on the patient and her parents to determine the diagnosis.Results: We identified a novel c. 1416_1437del (p.Ser473Argfs*43) mutation, as well as the previously identified c. 1499C>T (p.Ala500Val) mutation in TBC1D24, by using targeted next-generation sequencing. The novel mutation (inherited from the mother) is the first reported deletion mutation longer than 20 bp in TBC1D24. The p.Ala500Val mutation inherited from father has been reported in a German patient with infantile myoclonic, for whom results from the EEG and neuroimaging were normal. These two mutations resulted in the severe phenotypes observed in our patientConclusions: The identification of the novel TBC1D24 mutation and consequent complicated clinical manifestations suggest that patients with NCSE and ataxia demand more attention. We further recommend that genetic test should be administered to these patients to avoid genetic inheritance of this mutation.