单基因遗传性高血压致病基因突变研究内科学心血管专业论文.docxVIP

上海第二鞋科大学2000缓博士论文单基因遗传性高血征致病基因突变研究 上海第二鞋科大学2000缓博士论文 单基因遗传性高血征致病基因突变研究 摘 要 单基因遗传散高血压是指由某一个基因突变引越的符合孟德尔遗传方式的的～组 高斑压疾病。迄今为止，分子遗传学研究在引越人类盂德尔遗传式离血蕊的14个蘩因 中确定了致瘸突变。本研究救集了2个Liddle综合征、一个IIa鍪多发往内分泌腺癣瘸 (M斟堪a)积一个F穗誓病等霹个遗传经高艇压袈系、4铡散发游}瀣藤诊断韵Liddle综 合{委患蠢、42铡教发熬嗜镑缨照瘩惑学积一裂Go．on综合链患者。霹裰关致病蒸嚣 上皮钠邋道8贬单位基因(SCNNIB)和￥亚单位基[](SCNNl G)、RET愿瘰基嚣、a半 乳糖昔酶基因(GLA)、WNKl和WNK4基因等用直接DNA测序的方法进行了突变燕 查，结果发现1个Liddle综合征家系的致瘸突变为SCNNlB P618L，另～个Liddle综 合征家系中为SCNNlB基因P618S和D634H的联合突变，一个Liddle综合征散发性 患糟中突变为R566X；MEN*Ha家系中突变为RET C634G，42嗜铬细胞瘸患者中筛查 出1例突变为RET C634Y，1例为RET E632K：Gordon综合征患者未能在WNKl和 WNK4基因中发现突变；FabIy综合{芷家系中突变为GLA R301Q。通过对～些单基因 遗传萑高血嚣家系和散发往患者进行测序分析，确定了一擅高斑压患者的致病突变， 实现了蒸函诊断。在～个Liddie综合征家系中发现了SCNNtB蓉禹P618S和D634H 薪豹联合致襄突交，在一倒缮铬绥憨痃患者中发瑷了一个PET E632K凝突交。上述新 突燮故功能意义及其在裹蛊援发痰中斡《乍髑有待送一步磅突。 关键词：单基因遗传性赢血压 基因 突变 上海第二暖科大学2000缎博士论文Identification 上海第二暖科大学2000缎博士论文 Identification of the Genetic Mutations Causing Monogenic Forms of Hypertension Abstract Monogenic foml$of hypertension result from the mutations of single gene which play important role in the regulation of blood pressure variation。To穗lte，mutations in at least{4 genes have been identified to Cause various Mendelian hypertensive syndrome．These studies have added greatly to our understanding of the regulating mechanisms which affect blood pressure．Given the heterogeneity and diversity of mutations，there are perhaps some new mutations in the genes which cause hypertension in different population．1n this etu啦+molecular genetic defects of a few inhedtable disorders that CaUSeS hypertension，namely，Multiple endocrine neoplasta type 2，Liddle syndrome；Gordon syndrome and Fabry disease were investigated。We coi强cted two families with Liddle syndrome and four clinically diagnosed cases， one family with MEN-lie，one family wtth Fabty syndrome，42 DNA samples from patients with pheochromocytoma and one sporadic Case wi铂Gordon syndrome，To screen those mutations． the DNA sequence ofthe genes such as SCNNlB、SCNNlG、RET、GLA、WNKl and WNK4 were analyzed．Direct sequence