2例新生儿期起病癫痫患者的新发突变
De novo mutation in 2 patients with neonatal-onset epilepsy.
作者信息
Guella Ilaria, Huh Linda, McKenzie Marna B, Toyota Eric B, Bebin E Martina, Thompson Michelle L, Cooper Gregory M, Evans Daniel M, Buerki Sarah E, Adam Shelin, Van Allen Margot I, Nelson Tanya N, Connolly Mary B, Farrer Matthew J, Demos Michelle
机构信息
Centre for Applied Neurogenetics (CAN), Department of Medical Genetics (I.G., M.B.M., D.M.E., M.J.F.), Division of Neurology (L.H., E.B.T., S.E.B., M.B.C., M.D.), Department of Pediatrics, University of British Columbia and BC Children's Hospital, Vancouver, Canada; Department of Neurology (E.M.B.), University of Alabama at Birmingham; HudsonAlpha Institute for Biotechnology (M.L.T., G.M.C.), Huntsville, AL; Department of Medical Genetics (S.A., M.I.V.A.), University of British Columbia, Vancouver, Canada; and Departments of Pathology and Laboratory Medicine (T.N.N.), University of British Columbia and BC Children's Hospital, Vancouver, Canada.
出版信息
Neurol Genet. 2016 Nov 10;2(6):e120. doi: 10.1212/NXG.0000000000000120. eCollection 2016 Dec.
OBJECTIVE
We describe 2 additional patients with early-onset epilepsy with a de novo mutation.
METHODS
Whole-exome sequencing was performed in 2 unrelated patients with early-onset epilepsy and their unaffected parents. Genetic variants were assessed by comparative trio analysis. Clinical evolution, EEG, and neuroimaging are described. The phenotype and response to treatment was reviewed and compared to affected siblings in the original report.
RESULTS
We identified the same de novo mutation reported previously (c.G155A, p.R52H) in 2 additional patients with early-onset epilepsy. Similar to the original brothers described, both presented with tonic seizures in the first month of life. In the first patient, seizures responded to sodium channel blockers and her development was normal at 11 months. Patient 2 is a 15-year-old girl with treatment-resistant focal epilepsy, moderate intellectual disability, and autism. Carbamazepine (sodium channel blocker) was tried later in her course but not continued due to an allergic reaction.
CONCLUSIONS
The identification of a recurrent de novo mutation in 2 additional unrelated probands with early-onset epilepsy supports the role of p.R52H in disease pathogenesis. Affected carriers presented with similar early clinical phenotypes; however, this report expands the phenotype associated with this mutation which contrasts with the progressive course and early mortality of the siblings in the original report.
目的
我们描述另外2例患有新发突变的早发性癫痫患者。
方法
对2例无关的早发性癫痫患者及其未受影响的父母进行全外显子组测序。通过比较三联体分析评估基因变异。描述了临床病程、脑电图和神经影像学检查结果。回顾了表型及对治疗的反应，并与原始报告中的患病同胞进行了比较。
结果
我们在另外2例早发性癫痫患者中鉴定出先前报道的相同新发突变（c.G155A，p.R52H）。与最初描述的兄弟相似，这2例患者在出生后第一个月均出现强直发作。在第1例患者中，癫痫发作对钠通道阻滞剂有反应，其在11个月时发育正常。患者2是一名15岁女孩，患有耐药性局灶性癫痫、中度智力障碍和自闭症。在其病程后期试用了卡马西平（钠通道阻滞剂），但因过敏反应未继续使用。
结论
在另外2例无关的早发性癫痫先证者中鉴定出复发性新发突变，支持p.R52H在疾病发病机制中的作用。受影响的携带者表现出相似的早期临床表型；然而，本报告扩展了与该突变相关的表型，这与原始报告中同胞的进行性病程和早期死亡形成对比。
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