PRRT2 gene mutations associated with infantile convulsions induced by sucking and the genotype-phenotype correlation.
PRRT2 gene mutations associated with infantile convulsions induced by sucking and the genotype-phenotype correlation.
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PRRT2基因突变与吸吮诱发婴儿惊厥的相关性及基因型-表型相关性
DOI：
10.3389/fneur.2022.836048
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发表时间：
2022
影响因子：
3.4
通讯作者：
Yi, Yong-Hong
中科院分区：
文献类型：
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作者：
Liu, De-Tian;Tang, Xue-Qing;Wan, Rui-Ping;Luo, Sheng;Guan, Bao-Zhu;Li, Bin;Liu, Li-Hong;Li, Bing-Mei;Liu, Zhi-Gang;Xie, Long-Shan;Yi, Yong-Hong
PRRT2是自限性家族性新生儿-婴儿癫痫、阵发性运动诱导性运动障碍、阵发性运动诱导性运动障碍伴婴儿惊厥的主要致病基因。自主运动的触发点在青春期和成年期很明显，但婴儿的触发点还不清楚。为下一代定向测序(NGS)设计的基因小组被用来筛查45例婴儿惊厥队列中的遗传异常。通过基于归一化覆盖深度的计算方法检测拷贝数变化，并通过实时定量聚合酶链式反应(RT-qPCR)方法进行验证。分析PRRT2突变基因的基因型-表型相关性。在一名因用力吸吮导致婴儿惊厥的儿童中发现了PRRT2杂合子缺失。癫痫发作发生在喂养行为从母乳到配方奶粉的转变过程中，导致饥饿和猛烈的吮吸。发作期脑电记录了局灶性癫痫发作，这为携带PRRT2突变的婴儿癫痫发作提供了直接证据。通过缩短摄食间隔时间和延长摄食持续时间，改变摄食行为后，惊厥很快停止。对我们以前报告的PRRT2突变病例的数据重新分析显示，18名患者中有6名(33.3%)在喂养过程中出现婴儿惊厥或婴儿非惊厥发作。这些突变包括两个截断突变(c.579dupA/p.Glu194Argfs*6和c.649dupC/p.Arg217Pros*8)，在三个受影响的个体中都发现了这两个突变。这项研究表明，喂养，特别是猛烈的吮吸，可能是触发因素，并强调了喂养行为在预防PRRT2突变婴儿癫痫发作中的重要性。在吸吮诱发的婴儿惊厥患者中发现PRRT2单倍体不足突变提示潜在的基因-表型相关性。
PRRT2 is a major causative gene for self-limited familial neonatal-infantile epilepsy, paroxysmal kinesigenic dyskinesia, and paroxysmal kinesigenic dyskinesia with infantile convulsions. Voluntary movement trigger is prominent in adolescence and adulthood, but the triggers are unknown in infants. A gene panel designed for targeted next-generation sequencing (NGS) was used to screen genetic abnormalities in a cohort of 45 cases with infantile convulsions. The copy number variation was detected by a computational method based on the normalized depth of coverage and validated by a quantitative real-time polymerase chain reaction (RT-qPCR) method. The genotype-phenotype correlation of the PRRT2 mutation gene was analyzed. A de novo heterozygous PRRT2 deletion was identified in a child who had infantile convulsions induced by vigorous sucking. Seizures happened during the change of feeding behavior from breast to formula, which led to hungry and vigorous sucking. Ictal electroencephalograms recorded seizures with focal origination, which provided direct evidence of epileptic seizures in infants with PRRT2 mutations. Seizures stopped soon after the feeding behavior was changed by reducing feeding interval time and extending feeding duration. Data reanalysis on our previously reported cases with PRRT2 mutations showed that six of 18 (33.3%) patients had infantile convulsions or infantile non-convulsion seizures during feeding. The mutations included two truncating mutations (c.579dupA/p.Glu194Argfs*6, and c.649dupC/p.Arg217Profs*8) that were identified in each of the three affected individuals. This study suggests that feeding, especially vigorous sucking, is potentially a trigger and highlights the significance of feeding behavior in preventing seizures in infants with PRRT2 mutations. Identification of PRRT2 haploinsufficiency mutations in the patients with infantile convulsions induced by sucking suggested a potential genotype-phenotype correlation.
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影响因子：
--
作者：
Liu YT;Nian FS;Chou WJ;Tai CY;Kwan SY;Chen C;Kuo PW;Lin PH;Chen CY;Huang CW;Lee YC;Soong BW;Tsai JW
通讯作者：
Tsai JW
PRRT2缺陷通过调节小脑突触传递诱发阵发性运动性运动障碍
影响因子：
44.1
作者：
Tan GH;Liu YY;Wang L;Li K;Zhang ZQ;Li HF;Yang ZF;Li Y;Li D;Wu MY;Yu CL;Long JJ;Chen RC;Li LX;Yin LP;Liu JW;Cheng XW;Shen Q;Shu YS;Sakimura K;Liao LJ;Wu ZY;Xiong ZQ
通讯作者：
Xiong ZQ
影响因子：
30.8
作者：
Chen, Wan-Jin;Lin, Yu;Wu, Zhi-Ying
通讯作者：
Wu, Zhi-Ying
使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
4.3
作者：
Talevich E;Shain AH;Botton T;Bastian BC
通讯作者：
Bastian BC