本文選題：線粒體神經(jīng)胃腸腦肌病 + 胃腸蠕動障礙��； 參考：《山西醫(yī)科大學》2014年碩士論文

【摘要】：研究背景： 線粒體神經(jīng)胃腸腦肌病（mitochondrial neurogastrointestinal encephalomy-opathy, MNGIE）是一種罕見的多系統(tǒng)受累的常染色體隱性遺傳的線粒體疾病，其致病基因為TYMP。該基因突變可引起胸苷磷酸化酶（thymidine phosphorylase,TP)活性受損，導致核苷在血漿中和組織中蓄積以及線粒體功能障礙。臨床以神經(jīng)系統(tǒng)和胃腸系統(tǒng)受累為主要表現(xiàn)。主要通過檢測白細胞中TP活性和TYMP基因突變分析來明確診斷。 目的： 分析一個中國MNGIE家系的臨床、肌肉病理及遺傳學特征，并對患者及其家系成員行TYMP基因檢測，以明確致病突變位點。方法： 對山西醫(yī)科大學第一醫(yī)院神經(jīng)內(nèi)科臨床擬診為MNGIE的患者，進行詳盡的家系分析研究，收集先證者以及該家系成員詳盡的臨床資料和外周血標本，對先證者的臨床特點、影像學資料、肌肉活檢結(jié)果進行分析，并采用聚合酶鏈式反應進行TYMP基因突變分析。 結(jié)果： 1.先證者為45歲男性，20歲起病，以反復腹瀉為特征，后期表現(xiàn)為進行性的體重下降，查體可見先證者體型消瘦，眼瞼下垂及眼外肌麻痹，眼球各方向活動障礙，聽力下降及周圍神經(jīng)損害；頭顱MRI提示廣泛的腦白質(zhì)病變，，但基底節(jié)區(qū)和胼胝體區(qū)未受累。先證者父母為近親結(jié)婚。家系中其他成員無類似臨床表現(xiàn)。 2.先證者肌肉病理示：HE染色示肌纖維大小不一，可見數(shù)個紫紅色邊緣嗜堿性肌纖維，MGT染色可見多個破碎紅纖維，COX染色可見酶活性缺失纖維，SDH染色可見酶活性增強纖維。 3.先證者TYMP基因分析發(fā)現(xiàn)一個新的純合重復突變，即c.1193_1216dupGGGCGCTGCCGCTGGCGCTGGTGC，p.(Arg398_Val405dup)；該家系成員中III:1、III:3、IV:1、IV:6、V:2、V:3、V:4、V:5、V:7均為c.1193_1216dup的雜合突變。 結(jié)論： 1.先證者的臨床特點、血生化、影像學檢查及肌肉活檢結(jié)果，均符合典型MNGIE的表現(xiàn)。 2.先證者為c.1193_1216dup純合突變，該家系成員中有9例（III:1、III:3、IV:1、IV:6、V:2、V:3、V:4、V:5、V:7）均為c.1193_1216dup雜合突變，結(jié)合臨床表型及輔助檢查結(jié)果，該突變?yōu)楸炯蚁抵虏⊥蛔儭?3.先證者c.1193_1216dup純合突變所致MNGIE為國內(nèi)外首次報道。
[Abstract]:Background: mitochondrial neurogastroenteric encephalomyopathy (MNGIE) is a rare multisystem involving autosomal recessive mitochondrial disease. The mutation of this gene can damage the activity of thymidine phosphorylase TP, lead to the accumulation of nucleoside in plasma and tissue and the dysfunction of mitochondria function. The main clinical manifestations were nervous system and gastrointestinal system involvement. The diagnosis was determined by detecting TP activity and TYMP gene mutation in leukocytes. Objective: to analyze the clinical, muscular pathological and genetic characteristics of a Chinese MNGIE family, and to detect the TYMP gene of the patients and their family members in order to identify the pathogenicity mutation sites. Methods: the patients of Department of Neurology, the first Hospital of Shanxi Medical University, who were clinically diagnosed as MNGIE, were analyzed and studied in detail, and the clinical data and peripheral blood samples of the proband and the members of the family were collected. The clinical features, imaging data, muscle biopsy results and TYMP gene mutation were analyzed by polymerase chain reaction (PCR). Results: 1. The proband was a 45-year-old male who had been sick since the age of 20, characterized by repeated diarrhea, with progressive weight loss in the later stage. The body examination showed that the proband was thin, the eyelid drooping and the extraocular muscle paralysis, and the movement of the eyeball in all directions. Hearing loss and peripheral nerve damage, cranial MRI showed extensive white matter lesions, but the basal ganglia and corpus callosum were not involved. The proband's parents were married for their close relatives. Other members of the family have no similar clinical manifestations. 2. The muscle pathology of the proband showed that the size of muscle fiber was different with the staining of% HE. MGT staining of several purplish red edge basophilic muscle fibers can be seen in several broken red fibers Cox staining can be seen enzyme activity missing fiber SDH staining can be seen enzyme activity enhancement fiber. 3. A new homozygous repeat mutation was found in proband TYMP gene analysis, I. e., c.119316pGGCGCTGCCGCTGCTGCTGCTGGTGCCf. (Arg398Val405dup). Conclusion: 1. The clinical features, blood biochemistry, imaging findings and muscle biopsy results of the proband were in accordance with the typical MNGIE findings. 2. The proband was a homozygous mutation of c.1193_1216dup. Nine of the members (III: 1 / III: 3IV: 1: 1) were c.1193_1216dup heterozygosity mutations. Combined with the clinical phenotypic and auxiliary examination results, the mutation was a pathogenic mutation of this family. MNGIE caused by homozygous mutation of proband c.1193_1216dup was first reported at home and abroad.
【學位授予單位】：山西醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R741

【參考文獻】

相關(guān)期刊論文 前2條

1 許二赫;張彌蘭;董會卿;;線粒體神經(jīng)胃腸型腦肌病[J];中風與神經(jīng)疾病雜志;2011年09期

2 許二赫;張彌蘭;董會卿;賈建平;;線粒體神經(jīng)胃腸型腦肌病的臨床和病理分析[J];中風與神經(jīng)疾病雜志;2013年05期

本文編號：2059617