Zhang Xuan, Huang Zhaoyang, Liu Jianghong, Li Mingyu, Zhao Xiaoling, Ye Jing, Wang Yuping
Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.
Beijing Key Laboratory of Neuromodulation, Beijing, China.
Front Neurol. 2021 Jun 22;12:641019. doi: 10.3389/fneur.2021.641019. eCollection 2021.
Mutations in the disheveled, Egl-10 and domain-containing protein 5 (DEPDC5) recently have been identified as a common cause of focal epilepsy syndromes. The association between phenotype and genotype of DEPDC5 mutation has not been adequately characterized. We studied four families with familial focal epilepsy carrying DEPDC5 mutations. Four novel DEPDC5 mutations were identified by next-generation sequencing, including two missense mutations (c.1729 >A and c.3260G>A), one splicing mutation (c.280-1G>A), and one frameshift mutation (c.515_516delinsT). We found that patients carrying different DEPDC5 mutation have different clinical manifestations. Incomplete penetrance is a prominent feature of DEPDC5-related epilepsy, with the rate of penetrance ranging from 25 to 100%. About 21.4% of patients with DEPDC5-related familial focal epilepsy are refractory to treatments. We further reviewed the correlation of genotype and phenotype in all previous literature regarding DEPDC5-related epilepsy. Our study suggested that the type of DEPDC5 mutation might provide important information for the prognosis evaluation.
蓬乱蛋白、Egl-10和含结构域蛋白5（DEPDC5）的突变最近被确定为局灶性癫痫综合征的常见病因。DEPDC5突变的表型与基因型之间的关联尚未得到充分描述。我们研究了四个携带DEPDC5突变的家族性局灶性癫痫家系。通过下一代测序鉴定出四个新的DEPDC5突变，包括两个错义突变（c.1729>A和c.3260G>A）、一个剪接突变（c.280-1G>A）和一个移码突变（c.515_516delinsT）。我们发现携带不同DEPDC5突变的患者有不同的临床表现。不完全外显是DEPDC5相关癫痫的一个突出特征，外显率在25%至100%之间。约21.4%的DEPDC5相关家族性局灶性癫痫患者对治疗无效。我们进一步回顾了以往所有关于DEPDC5相关癫痫的文献中基因型与表型的相关性。我们的研究表明，DEPDC5突变类型可能为预后评估提供重要信息。
