De novo FGF12 mutation in 2 patients with neonatal-onset epilepsy
De novo FGF12 mutation in 2 patients with neonatal-onset epilepsy
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DOI：
10.1212/nxg.0000000000000120
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发表时间：
2016-12-01
影响因子：
3.1
通讯作者：
Demos, Michelle
中科院分区：
文献类型：
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作者：
Guella, Ilaria;Huh, Linda;Demos, Michelle
目的：我们描述了2个额外的早发性癫痫患者与新生FGF 12 mutation.Methods：全外显子组测序进行了2个无关的早发性癫痫患者和他们的未受影响的父母。通过比较三重分析评估遗传变异。临床演变，脑电图和神经影像学的描述。表型和治疗反应进行了审查，并在原始report.Results：我们确定了相同的FGF 12从头突变报告（c.G155A，p.R52H）在2个额外的早发性癫痫患者。与最初描述的兄弟相似，两人在出生后的第一个月都出现了强直性癫痫发作。在第一名患者中，癫痫发作对钠通道阻滞剂有反应，她在11个月时发育正常。患者2是一名15岁女孩，患有难治性局灶性癫痫、中度智力残疾和自闭症。在她的疗程后期尝试了卡马西平（钠通道阻滞剂），但由于过敏反应而没有继续。结论：在另外2名不相关的早发性癫痫先证者中发现了复发性从头突变，支持了FGF 12 p.R52 H在疾病发病机制中的作用。受影响的携带者呈现出相似的早期临床表型;然而，本报告扩展了与这种突变相关的表型，这与原始报告中兄弟姐妹的进展过程和早期死亡率形成对比。
Objective: We describe 2 additional patients with early-onset epilepsy with a de novo FGF12 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 FGF12 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 FGF12 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.