Luo Han-Yu, Xie Ling-Ling, Hong Si-Qi, Li Xiu-Juan, Li Mei, Hu Yue, Ma Jian-Nan, Wu Peng, Zhong Min, Cheng Min, Li Ting-Song, Jiang Li
Department of Neurology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.
Chongqing Key Laboratory of Pediatrics, Chongqing, China.
Front Pediatr. 2021 May 10;9:676616. doi: 10.3389/fped.2021.676616. eCollection 2021.
To study the genetic and clinical characteristics of Chinese children with pathogenic proline-rich transmembrane protein 2 () gene-associated disorders. Targeted next generation sequencing (NGS) was used to identify pathogenic variations in Chinese children with epilepsy and/or kinesigenic dyskinesia. Patients with confirmed -associated disorders were monitored and their clinical data were analyzed. Forty-four patients with pathogenic variants were recruited. Thirty-five of them (79.5%) had heterozygous mutations, including 30 frameshifts, three missenses, one nonsense, and one splice site variant. The c.649dupC was the most common variant (56.8%). Eight patients (18.2%) showed whole gene deletions, and one patient (2.3%) had 16p11.2 microdeletion. Thirty-four cases (97.1%) were inherited and one case (2.9%) was . Forty patients were diagnosed with benign familial infantile epilepsy (BFIE), two patients had paroxysmal kinesigenic dyskinesia (PKD) and two had infantile convulsions and choreoathetosis (ICCA). Patients with whole gene deletions had a later remission than patients with heterozygous mutations (13.9 vs. 7.1 months, = 0.001). Forty-two patients were treated with antiseizure medications (ASMs). At last follow-up, 35 patients, including one who did not receive therapy, were asymptomatic, and one patient without ASMs died of status epilepticus at 12 months of age. One patient developed autism, and one patient showed mild developmental delay/intellectual disability. Our data suggested that patients with whole gene deletions could have more severe manifestations in -associated disorders. Conventional ASMs, especially Oxcarbazepine, showed a good treatment response.
研究中国患有富含脯氨酸跨膜蛋白2（PRRT2）基因相关疾病儿童的遗传和临床特征。采用靶向二代测序（NGS）来鉴定患有癫痫和/或运动诱发性运动障碍的中国儿童中的PRRT2致病性变异。对确诊为PRRT2相关疾病的患者进行监测并分析其临床数据。招募了44例具有PRRT2致病性变异的患者。其中35例（79.5%）为杂合突变，包括30个移码突变、3个错义突变、1个无义突变和1个剪接位点变异。c.649dupC是最常见的变异（56.8%）。8例患者（18.2%）表现为全基因缺失，1例患者（2.3%）有16p11.2微缺失。34例（97.1%）为遗传性，1例（2.9%）为散发性。40例患者被诊断为良性家族性婴儿癫痫（BFIE），2例患者患有阵发性运动诱发性运动障碍（PKD），2例患有婴儿惊厥和舞蹈手足徐动症（ICCA）。全基因缺失的患者比杂合突变的患者缓解时间更晚（13.9个月对7.1个月，P = 0.001）。42例患者接受了抗癫痫药物（ASM）治疗。在最后一次随访时，35例患者（包括1例未接受治疗的患者）无症状，1例未接受ASM治疗的患者在12个月龄时死于癫痫持续状态。1例患者出现自闭症，1例患者表现为轻度发育迟缓/智力残疾。我们的数据表明，全基因缺失的患者在PRRT2相关疾病中可能有更严重的表现。传统的ASM，尤其是奥卡西平，显示出良好的治疗反应。
