Genetic and phenotypic analyses of PRRT2 positive and negative paroxysmal kinesigenic dyskinesia.

IF 5.4 3区材料科学 Q2 CHEMISTRY, PHYSICAL

ACS Applied Energy Materials Pub Date : 2024-01-18 eCollection Date: 2024-01-01 DOI:10.1177/17562864231224110

Yingying Zhang, Jiechuan Ren, Tianhua Yang, Weixi Xiong, Linyuan Qin, Dongmei An, Fayun Hu, Dong Zhou

{"title":"Genetic and phenotypic analyses of PRRT2 positive and negative paroxysmal kinesigenic dyskinesia.","authors":"Yingying Zhang, Jiechuan Ren, Tianhua Yang, Weixi Xiong, Linyuan Qin, Dongmei An, Fayun Hu, Dong Zhou","doi":"10.1177/17562864231224110","DOIUrl":null,"url":null,"abstract":"Background: Paroxysmal kinesigenic dyskinesia (PKD) is a rare neurological disorder, characterized by attacks of involuntary movements triggered by sudden action. Variants in proline-rich transmembrane protein 2 (PRRT2) are the most common genetic cause of PKD.Objective: The objective was to investigate the clinical and genetic characteristics of PKD and to establish genotype-phenotype correlations.Methods: We enrolled 219 PKD patients, documented their clinical information and performed PRRT2 screening using Sanger sequencing. Whole exome sequencing was performed on 49 PKD probands without PRRT2 variants. Genotype-phenotype correlation analyses were conducted on the probands.Results: Among 219 PKD patients (99 cases from 39 families and 120 sporadic cases), 16 PRRT2 variants were identified. Nine variants (c.879+4A>G, c.879+5G>A, c.856G>A, c.955G>T, c.884G>C, c.649C>T, c.649dupC, c.649delC and c.696_697delCA) were previously known, while seven were novel (c.367_403del, c.347_348delAA, c.835C>T, c.116dupC, c.837_838insC, c.916_937del and c.902G>A). The mean interval from onset to diagnosis was 7.94 years. Compared to patients without PRRT2 variants, patients with the variants were more likely to have a positive family history, an earlier age of onset and a higher prevalence of falls during pre-treatment attacks (27.14% versus 8.99%, respectively). Patients with truncated PRRT2 variants tend to have bilateral attacks. We identified two transmembrane protein 151A (TMEM151A) variants including a novel variant (c.368G>C) and a reported variant (c.203C>T) in two PRRT2-negative probands with PKD.Conclusion: These findings provide insights on the clinical characteristics, diagnostic timeline and treatment response of PKD patients. PKD patients with truncated PRRT2 variants may tend to have more severe paroxysmal symptoms. This study expands the spectrum of PRRT2 and TMEM151A variants. Carbamazepine and oxcarbazepine are both used as a first-line treatment choice for PKD patients.","PeriodicalId":4,"journal":{"name":"ACS Applied Energy Materials","volume":"17 ","pages":"17562864231224110"},"PeriodicalIF":5.4000,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10798112/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Energy Materials","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/17562864231224110","RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Paroxysmal kinesigenic dyskinesia (PKD) is a rare neurological disorder, characterized by attacks of involuntary movements triggered by sudden action. Variants in proline-rich transmembrane protein 2 (PRRT2) are the most common genetic cause of PKD.

Objective: The objective was to investigate the clinical and genetic characteristics of PKD and to establish genotype-phenotype correlations.

Methods: We enrolled 219 PKD patients, documented their clinical information and performed PRRT2 screening using Sanger sequencing. Whole exome sequencing was performed on 49 PKD probands without PRRT2 variants. Genotype-phenotype correlation analyses were conducted on the probands.

Results: Among 219 PKD patients (99 cases from 39 families and 120 sporadic cases), 16 PRRT2 variants were identified. Nine variants (c.879+4A>G, c.879+5G>A, c.856G>A, c.955G>T, c.884G>C, c.649C>T, c.649dupC, c.649delC and c.696_697delCA) were previously known, while seven were novel (c.367_403del, c.347_348delAA, c.835C>T, c.116dupC, c.837_838insC, c.916_937del and c.902G>A). The mean interval from onset to diagnosis was 7.94 years. Compared to patients without PRRT2 variants, patients with the variants were more likely to have a positive family history, an earlier age of onset and a higher prevalence of falls during pre-treatment attacks (27.14% versus 8.99%, respectively). Patients with truncated PRRT2 variants tend to have bilateral attacks. We identified two transmembrane protein 151A (TMEM151A) variants including a novel variant (c.368G>C) and a reported variant (c.203C>T) in two PRRT2-negative probands with PKD.

Conclusion: These findings provide insights on the clinical characteristics, diagnostic timeline and treatment response of PKD patients. PKD patients with truncated PRRT2 variants may tend to have more severe paroxysmal symptoms. This study expands the spectrum of PRRT2 and TMEM151A variants. Carbamazepine and oxcarbazepine are both used as a first-line treatment choice for PKD patients.

查看原文本刊更多论文

PRRT2 阳性和阴性阵发性运动障碍的遗传和表型分析。

背景：阵发性运动障碍（PKD）是一种罕见的神经系统疾病，其特征是由突然动作引发的不自主运动。富脯氨酸跨膜蛋白 2（PRRT2）的变异是 PKD 最常见的遗传病因：目的：研究 PKD 的临床和遗传特征，并建立基因型与表型之间的相关性：我们招募了219名PKD患者，记录了他们的临床信息，并使用桑格测序法进行了PRRT2筛查。对49名没有PRRT2变异的PKD疑似患者进行了全外显子测序。结果显示，在219名PKD患者中（99人），PRRT2变异率为0.9%，而PKD患者的PRRT2变异率为0.9%：结果：在219例PKD患者中（99例来自39个家族，120例为散发性病例），发现了16个PRRT2变异。9个变异（c.879+4A>G、c.879+5G>A、c.856G>A、c.955G>T、c.884G>C、c.649C>T、c.649dupC、c.649delC和c.696697delCA），而 7 个是新发现的（c.367_403del、c.347_348delAA、c.835C>T、c.116dupC、c.837_838insC、c.916_937del 和 c.902G>A）。从发病到确诊的平均间隔时间为 7.94 年。与没有PRRT2变异体的患者相比，有变异体的患者更可能有阳性家族史，发病年龄更早，在治疗前发作时跌倒的发生率更高（分别为27.14%和8.99%）。具有截短PRRT2变异体的患者往往双侧发病。我们在两名PRRT2阴性的PKD患者中发现了两个跨膜蛋白151A（TMEM151A）变异体，包括一个新变异体（c.368G>C）和一个已报道的变异体（c.203C>T）：这些发现为PKD患者的临床特征、诊断时限和治疗反应提供了启示。具有截短PRRT2变异的PKD患者可能会有更严重的阵发性症状。这项研究扩大了PRRT2和TMEM151A变体的范围。卡马西平和奥卡西平都是PKD患者的一线治疗选择。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

ACS Applied Energy Materials Materials Science-Materials Chemistry

CiteScore

10.30

自引率

6.20%

发文量

1368

期刊介绍： ACS Applied Energy Materials is an interdisciplinary journal publishing original research covering all aspects of materials, engineering, chemistry, physics and biology relevant to energy conversion and storage. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important energy applications.