TUBB2B基因变异导致的灰质异位症合并癫痫1例报告并文献复习

Report of a case of grey matter heterotopia combined with epilepsy due to TUBB2B gene variant and review of literature

目的报道1例TUBB2B基因新生杂合错义突变导致的灰质异位患者临床表型及基因突变位点,拓展TUBB2B突变的表型谱和突变谱。方法收集2017年7月就诊于空军军医大学第一附属医院神经内科的1例TUBB2B突变患者,分析其临床特征和突变位点,并对既往研究进行回顾总结。结果患者男性,18岁起病,主要表现为癫痫发作、左手精细动作不良和空间想象力差。磁共振成像提示右额叶底部结节状灰质异位,右侧额顶颞部局部脑回、脑沟浅平。全外显子基因检测结果提示该患者TUBB2B基因c.776 C>T(p.Pro259Leu)杂合错义突变,患者的父母均为野生型。该突变位点位于tubulin和tubulin-c结构域之间,未影响到重要结构域的功能。使用丙戊酸镁联合左乙拉西坦治疗后,患者的癫痫症状得到明显控制,至今已有3年未出现癫痫发作。结论TUBB2B基因c.776 C>T(p.Pro259Leu)杂合错义突变是导致灰质异位的新生错义突变。患者预后良好,两种抗癫痫药物联合治疗可完全控制癫痫发作。

Objective To report the clinical phenotype and mutation site of a patient with grey matter heterotopia caused by a de novo heterozygous missense mutation in the TUBB2B gene,and to expand the phenotypic and mutational spectrum of TUBB2B mutations.Methods One patient with TUBB2B mutation who presented to the Department of Neurology,the First Affiliated Hospital of Air Force Medical University in July 2017 was collected and analyzed for clinical features and mutation site,and a review of previous studies was performed.Results The male patient started at the age of 18 and presented mainly with seizures,poor left-handed fine motor skills and poor spatial imagination.Magnetic resonance imaging showed nodular grey matter heterotopia in the right cerebral hemisphere,right frontoparietal-temporal localized cerebral gyrus,and cerebral sulcus shallow flat.The whole exon gene test suggested a heterozygous missense mutation in the TUBB2B gene:c.776 C>T(p.Pro259Leu),which was wild-type in both of his parents.The mutation site was located between the tubulin and tubulin-c structural domains and did not affect the function of the essential structural domain.After treatment with magnesium valproate in combination with levetiracetam,the patient′s seizure symptoms were significantly controlled and he has been seizure-free for 3 years now.Conclusions The TUBB2B gene c.776 C>T(p.Pro259Leu)heterozygous missense mutation is a novel missense mutation causing grey matter heterotopia.The patient had a good prognosis,and the combination of two antiepileptic drugs resulted in complete seizure control.