Zhou Qin, Wang Jingwei, Xia Li, Li Rong, Zhang Qiumin, Pan Songqing
Department of Neurology, Renmin Hospital, Wuhan University, Wuhan, China.
Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, China.
Front Neurol. 2021 Sep 20;12:736977. doi: 10.3389/fneur.2021.736977. eCollection 2021.
Toothbrushing epilepsy is a rare form of reflex epilepsy (RE) with sporadic incidence. To characterize the genetic profile of reflex epilepsy patients with tooth brushing-induced seizures in a Chinese family. Solo clinical whole-exome sequencing (WES) of the proband, a 37-year-old Chinese man, was performed to characterize the genetic etiology of toothbrushing epilepsy. Mutations in the maternal X-linked synapsin 1 (SYN1) identified in the proband and his family members were confirmed by Sanger sequencing. The pathogenicity of these mutations was determined using in silico analysis. The proband had four episodes of toothbrushing-induced seizures. The semiology included nausea, twitching of the right side of the mouth and face, followed by a generalized tonic-clonic seizure (GTCS). The proband's elder maternal uncle had three toothbrushing-induced epileptic seizures at the age of 26. The proband's younger maternal uncle had no history of epileptic seizures but had a learning disability and aggressive tendencies. We identified a deleterious nonsense mutation, c.1807C>T (p.Q603Ter), in exon 12 of the gene (NM_006950), which can result in a truncated phosphoprotein with altered flexibility and hydropathicity. This novel mutation has not been reported in the 1000G, EVS, ExAC, gnomAD, or HGMD databases. We identified a novel X-linked exon 12 mutant gene in a Chinese family with toothbrushing epilepsy. Our findings provide novel insights into the mechanism of this complex form of reflex epilepsy that could potentially be applied in disease diagnosis.
刷牙性癫痫是反射性癫痫（RE）的一种罕见形式，发病率呈散发性。为了明确一个中国家庭中刷牙诱发癫痫发作的反射性癫痫患者的基因特征。对一名37岁的中国男性先证者进行了单例临床全外显子组测序（WES），以明确刷牙性癫痫的遗传病因。通过桑格测序法证实了先证者及其家庭成员中母系X连锁突触素1（SYN1）的突变。使用计算机分析确定这些突变的致病性。先证者有4次刷牙诱发的癫痫发作。发作症状包括恶心、右侧口角和面部抽搐，随后出现全身性强直阵挛发作（GTCS）。先证者的大舅在26岁时出现过3次刷牙诱发的癫痫发作。先证者的小舅没有癫痫发作史，但有学习障碍和攻击倾向。我们在基因（NM_006950）的第12外显子中发现了一个有害的无义突变，c.1807C>T（p.Q603Ter），该突变可导致截短的磷酸蛋白，其柔韧性和亲水性发生改变。这个新突变在1000G、EVS、ExAC、gnomAD或HGMD数据库中均未报道。我们在一个患有刷牙性癫痫的中国家庭中发现了一个新的X连锁第12外显子突变基因。我们的研究结果为这种复杂形式的反射性癫痫的发病机制提供了新的见解，可能应用于疾病诊断。
