PARK14突变帕金森综合征3例并临床异质性文献回顾

发布时间：2018-04-25 02:22

  本文选题：PARK14 + PLA2G6　； 参考：《山东大学》2017年硕士论文

【摘要】：目的:总结并分析3例PARK14突变帕金森综合征患者的临床资料、基因突变致病性及表型-基因型关联性。对PARK14相关帕金森病的临床异质性进行回顾与讨论,为临床诊断、选择治疗方式及判断预后提供有力的支持。方法:收集2014年12月至2016年10月期间就诊于山东大学齐鲁医院神经内科的3例PARK14突变帕金森综合征患者的临床资料。采用《2015年运动障碍协会(MDS)帕金森病临床诊断指南》对3例患者进行帕金森综合征/帕金森病的诊断。采用OMIM、HGMD Pro等数据库对3名患者具有的基因突变进行突变注释,采用Polyphen2.0、SIFT、MutationTaster等软件对突变致病性进行预测,并结合《2015年美国医学遗传学及基因组学学院(ACMG)测序变异解读标准与指南》对突变进行致病性分析,结合OMIM、HGMD pro数据库等对表型-基因型关联性进行分析。回顾Pubmed数据库收录的PARK14相关帕金森病相关文献,总结并讨论PARK14相关帕金森病的临床异质性。结果:1.本研究共收录3例PARK14突变帕金森综合征患者(Ⅰ-Ⅲ),其中男性1例(Ⅰ),女性2例(Ⅱ、Ⅲ)。结合临床资料、基因突变致病性及表型-基因型关联性分析结果,3例患者分别临床诊断为早发型原发性帕金森病(Ⅰ),PARK14相关帕金森病(Ⅱ),早发型肌张力障碍-帕金森综合征(Ⅲ)。2.基因突变致病性分析示:PARK14(PLA2G6)相关突变中,c.2255CG为疑似良性突变,c.991GT为致病突变,c.967GA、c.1918GA为临床意义未明突变。PRKRA基因的c.704GC突变为疑似良性突变。3.回顾7种PARK14相关帕金森病中的纯合突变及复合杂合突变类型,对其临床异质性进行分析,发现c.2222GA、c.991GT纯合突变为报道较多的突变类型。各突变类型均为早发型伴或不伴肌张力障碍的帕金森综合征。较多见的临床症状包括运动迟缓、肌强直、震颤、肌张力障碍、眼部症状、言语障碍、步态障碍、认知功能损害、精神症状及自主神经功能障碍等。具有较强致病性突变(如c.2222GA纯合突变及各类复合杂合突变)的患者,其起病相对较早,病情进展快,病情较严重,除帕金森症状外还伴有多种额外的神经精神症状。具有相对较弱致病性突变(如c.991GT纯合突变)的患者,起病年龄相对较晚,病情进展缓慢,多表现为帕金森症状,预后较好。结论:PARK14相关帕金森综合征临床上较少见,不同突变类型其临床特征之间具有很大差异,其临床诊断需结合临床资料及基因检测结果进行综合分析。明确其临床异质性有助于早期发现并进行基因检测,同时为选择合适的治疗方式与预测预后提供指导。
[Abstract]:Objective: to summarize and analyze the clinical data, gene mutation pathogenicity and phenotypic correlation in 3 patients with Parkinson's syndrome (PD) with PARK14 mutation. The clinical heterogeneity of PARK14 associated Parkinson's disease was reviewed and discussed in order to provide strong support for clinical diagnosis, choice of treatment and prognosis. Methods: the clinical data of 3 patients with PARK14 mutation Parkinson's syndrome were collected from December 2014 to October 2016 in the Department of Neurology, Qilu Hospital, Shandong University. Three cases of Parkinson's syndrome / Parkinson's disease were diagnosed by using the guidelines for clinical diagnosis of Parkinson's disease (MDS). OMIMMD Pro and other databases were used to annotate the mutations in 3 patients, and the mutation pathogenicity was predicted by Polyphen2.0 SIFTX mutation Taster and so on. The pathogenicity of the mutation was analyzed by combining with the Standard and Guide of ACMG sequencing variation of the American College of Medical Genetics and Genomics 2015, and the phenotypic and genotypic correlation was analyzed with OMIMN HGMD pro database. The clinical heterogeneity of PARK14 related Parkinson's disease (PD) was reviewed and discussed in Pubmed database. The result is 1: 1. Three patients with Parkinson's syndrome (鈪，

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