本文選題：PARK14 + PLA2G6�。� 參考：《山東大學(xué)》2017年碩士論文

【摘要】：目的:總結(jié)并分析3例PARK14突變帕金森綜合征患者的臨床資料、基因突變致病性及表型-基因型關(guān)聯(lián)性。對PARK14相關(guān)帕金森病的臨床異質(zhì)性進(jìn)行回顧與討論,為臨床診斷、選擇治療方式及判斷預(yù)后提供有力的支持。方法:收集2014年12月至2016年10月期間就診于山東大學(xué)齊魯醫(yī)院神經(jīng)內(nèi)科的3例PARK14突變帕金森綜合征患者的臨床資料。采用《2015年運(yùn)動障礙協(xié)會(MDS)帕金森病臨床診斷指南》對3例患者進(jìn)行帕金森綜合征/帕金森病的診斷。采用OMIM、HGMD Pro等數(shù)據(jù)庫對3名患者具有的基因突變進(jìn)行突變注釋,采用Polyphen2.0、SIFT、MutationTaster等軟件對突變致病性進(jìn)行預(yù)測,并結(jié)合《2015年美國醫(yī)學(xué)遺傳學(xué)及基因組學(xué)學(xué)院(ACMG)測序變異解讀標(biāo)準(zhǔn)與指南》對突變進(jìn)行致病性分析,結(jié)合OMIM、HGMD pro數(shù)據(jù)庫等對表型-基因型關(guān)聯(lián)性進(jìn)行分析�；仡橮ubmed數(shù)據(jù)庫收錄的PARK14相關(guān)帕金森病相關(guān)文獻(xiàn),總結(jié)并討論P(yáng)ARK14相關(guān)帕金森病的臨床異質(zhì)性。結(jié)果:1.本研究共收錄3例PARK14突變帕金森綜合征患者(Ⅰ-Ⅲ),其中男性1例(Ⅰ),女性2例(Ⅱ、Ⅲ)。結(jié)合臨床資料、基因突變致病性及表型-基因型關(guān)聯(lián)性分析結(jié)果,3例患者分別臨床診斷為早發(fā)型原發(fā)性帕金森病(Ⅰ),PARK14相關(guān)帕金森病(Ⅱ),早發(fā)型肌張力障礙-帕金森綜合征(Ⅲ)。2.基因突變致病性分析示:PARK14(PLA2G6)相關(guān)突變中,c.2255CG為疑似良性突變,c.991GT為致病突變,c.967GA、c.1918GA為臨床意義未明突變。PRKRA基因的c.704GC突變?yōu)橐伤屏夹酝蛔儭?.回顧7種PARK14相關(guān)帕金森病中的純合突變及復(fù)合雜合突變類型,對其臨床異質(zhì)性進(jìn)行分析,發(fā)現(xiàn)c.2222GA、c.991GT純合突變?yōu)閳蟮垒^多的突變類型。各突變類型均為早發(fā)型伴或不伴肌張力障礙的帕金森綜合征。較多見的臨床癥狀包括運(yùn)動遲緩、肌強(qiáng)直、震顫、肌張力障礙、眼部癥狀、言語障礙、步態(tài)障礙、認(rèn)知功能損害、精神癥狀及自主神經(jīng)功能障礙等。具有較強(qiáng)致病性突變(如c.2222GA純合突變及各類復(fù)合雜合突變)的患者,其起病相對較早,病情進(jìn)展快,病情較嚴(yán)重,除帕金森癥狀外還伴有多種額外的神經(jīng)精神癥狀。具有相對較弱致病性突變(如c.991GT純合突變)的患者,起病年齡相對較晚,病情進(jìn)展緩慢,多表現(xiàn)為帕金森癥狀,預(yù)后較好。結(jié)論:PARK14相關(guān)帕金森綜合征臨床上較少見,不同突變類型其臨床特征之間具有很大差異,其臨床診斷需結(jié)合臨床資料及基因檢測結(jié)果進(jìn)行綜合分析。明確其臨床異質(zhì)性有助于早期發(fā)現(xiàn)并進(jìn)行基因檢測,同時為選擇合適的治療方式與預(yù)測預(yù)后提供指導(dǎo)。
[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，

本文編號：1799340