The Genotype and Phenotype of Proline-Rich Transmembrane Protein 2 Associated Disorders in Chinese Children.
The Genotype and Phenotype of Proline-Rich Transmembrane Protein 2 Associated Disorders in Chinese Children.
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DOI：
10.3389/fped.2021.676616
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发表时间：
2021
影响因子：
2.6
通讯作者：
Jiang L
中科院分区：
文献类型：
--
作者：
Luo HY;Xie LL;Hong SQ;Li XJ;Li M;Hu Y;Ma JN;Wu P;Zhong M;Cheng M;Li TS;Jiang L
目的：研究中国儿童致病性富含脯氨酸跨膜蛋白2（PRRT 2）基因相关疾病的遗传学和临床特征。研究方法：采用靶向下一代测序（NGS）技术鉴定中国癫痫和/或运动诱发性运动障碍儿童的致病性PRRT 2变异。对确诊PRRT 2相关疾病的患者进行监测，并分析其临床数据。结果：招募了44名具有致病性PRRT 2变异体的患者。其中35例（79.5%）有杂合突变，包括30个移码，3个错义，1个无义和1个剪接位点变异。c.649dupC是最常见的变异（56.8%）。全基因缺失8例（18.2%），16p11.2微缺失1例（2.3%）。34例（97.1%）为遗传性，1例（2.9%）为新发。40例患者被诊断为良性家族性婴儿癫痫（BFIE），2例患者有阵发性运动诱发性运动障碍（PKD），2例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有更晚的缓解（13.9 vs. 7.1个月，P = 0.001）。42例患者接受抗癫痫药物（ASMs）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例无ASM的患者在12个月大时死于癫痫持续状态。1例患者出现自闭症，1例患者出现轻度发育迟缓/智力残疾。结论：我们的数据表明，全基因缺失的患者可能有更严重的PRRT 2相关疾病的表现。传统的ASM，特别是奥卡西平，表现出良好的治疗反应。
Objectives: To study the genetic and clinical characteristics of Chinese children with pathogenic proline-rich transmembrane protein 2 (PRRT2) gene-associated disorders. Methods: Targeted next generation sequencing (NGS) was used to identify pathogenic PRRT2 variations in Chinese children with epilepsy and/or kinesigenic dyskinesia. Patients with confirmed PRRT2-associated disorders were monitored and their clinical data were analyzed. Results: Forty-four patients with pathogenic PRRT2 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 de novo. 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, P = 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. Conclusion: Our data suggested that patients with whole gene deletions could have more severe manifestations in PRRT2-associated disorders. Conventional ASMs, especially Oxcarbazepine, showed a good treatment response.
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影响因子：
5.6
作者：
Labate, Angelo;Tarantino, Patrizia;Gambardella, Antonio
通讯作者：
Gambardella, Antonio
影响因子：
3.9
作者：
Schubert, Julian;Paravidino, Roberta;Weber, Yvonne G.
通讯作者：
Weber, Yvonne G.
影响因子：
158.5
作者：
Weiss, Lauren A.;Shen, Yiping;Daly, Mark J.
通讯作者：
Daly, Mark J.
影响因子：
1.9
作者：
Caraballo, RH;Cersósimo, RO;Fejerman, N
通讯作者：
Fejerman, N
DOI：
10.1093/brain/awy051
发表时间：
2018-04-01
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Fruscione F;Valente P;Sterlini B;Romei A;Baldassari S;Fadda M;Prestigio C;Giansante G;Sartorelli J;Rossi P;Rubio A;Gambardella A;Nieus T;Broccoli V;Fassio A;Baldelli P;Corradi A;Zara F;Benfenati F
通讯作者：
Benfenati F