Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China.
Department of Pediatrics, Linyi People's Hospital Affiliated to Shandong University, Linyi, China.
Brain Behav. 2020 May;10(5):e01597. doi: 10.1002/brb3.1597. Epub 2020 Mar 31.
Point and copy number variant mutations in the PRRT2 gene have been identified in a variety of paroxysmal disorders and different types of epilepsy. In this study, we analyzed the phenotypes and PRRT2-related mutations in Chinese epilepsy children.
A total of 492 children with epilepsy were analyzed by whole exome sequencing (WES) and low-coverage massively parallel CNV sequencing (CNV-seq) to find the single nucleotide variants and copy number variations (CNVs). And quantitative polymerase chain reaction was utilized to verify the CNVs. Their clinical information was followed up.
We found PRRT2-related mutations in 19 patients (10 males and nine females, six sporadic cases and 13 family cases). Twelve point mutations, four whole gene deletion, and three 16p11.2 deletions were detected. The clinical features of 39 patients in 19 families included one early childhood myoclonic epilepsy (ECME), one febrile seizure (FS), two infantile convulsions with paroxysmal choreoathetosis (ICCA), six paroxysmal kinesigenic dyskinesias (PKD), 12 benign infantile epilepsy (BIE), and 17 benign familial infantile epilepsy (BFIE). All patients had normal brain MRI. Interictal EEG showed only one patient had generalized polyspike wave and five patients had focal transient discharges. Focal seizures originating in the frontal region were recorded in one patient, two from the temporal region, and two from the occipital region. Most patients were treated effectively with VPA or OXC, and the child with myoclonic seizures was not sensitive to antiepileptic drugs.
PRRT2 mutations can be inherited or de novo, mainly inherited. The clinical spectrum of PRRT2 mutation includes BIE, BFIE, ICCA, PKD, FS, and ECME. The PRRT2-related mutations contained point mutation, whole gene deletion and 16p11.2 deletions, and large microdeletion mutations mostly de novo. It is the first report of PRRT2 mutation found in ECME. Our report expands the mutation and clinical spectrum of PRRT2-related epilepsy.
PRRT2 基因中的点突变和拷贝数变异突变已在各种发作性疾病和不同类型的癫痫中被发现。在这项研究中，我们分析了中国癫痫患儿的表型和 PRRT2 相关突变。
通过全外显子组测序（WES）和低覆盖度大规模平行 CNV 测序（CNV-seq）对 492 名癫痫患儿进行分析，以寻找单核苷酸变异和拷贝数变异（CNVs）。并利用定量聚合酶链反应验证 CNVs。对他们的临床信息进行了随访。
我们在 19 名患者（男 10 例，女 9 例，散发性 6 例，家族性 13 例）中发现了 PRRT2 相关突变。检测到 12 个点突变，4 个全基因缺失和 3 个 16p11.2 缺失。19 个家系中的 39 例患者的临床特征包括 1 例早发性儿童肌阵挛性癫痫（ECME）、1 例热性惊厥（FS）、2 例婴儿发作性肌阵挛伴舞蹈手足徐动症（ICCA）、6 例发作性运动诱发性运动障碍（PKD）、12 例良性婴儿癫痫（BIE）和 17 例良性家族性婴儿癫痫（BFIE）。所有患者的脑 MRI 均正常。发作间期脑电图仅显示 1 例患者出现全面性多棘慢波，5 例患者出现局灶性短暂放电。1 例患者记录到起源于额区的局灶性发作，2 例来自颞区，2 例来自枕区。大多数患者经 VPA 或 OXC 治疗有效，肌阵挛发作的患儿对抗癫痫药物不敏感。
PRRT2 突变可遗传或新生，主要为遗传。PRRT2 突变的临床谱包括 BIE、BFIE、ICCA、PKD、FS 和 ECME。PRRT2 相关突变包含点突变、全基因缺失和 16p11.2 缺失，大片段微缺失突变主要为新生。这是首次报道 PRRT2 突变与 ECME 有关。我们的报告扩展了 PRRT2 相关癫痫的突变和临床谱。
