一家族性高胆固醇血症家系临床表型及低密度脂蛋白受体基因突变研究
发布时间：2018-03-11 16:14
本文选题：基因 切入点：家族性 出处：《贵州医科大学》2017年硕士论文 论文类型：学位论文
【摘要】：目的:探讨家族性高胆固醇血症(familial hypercholesterolemia,FH)的分子病理机制,分析FH患者基因突变位点与临床表型之间的关系。方法:以一FH家系为研究对象,对其成员进行体格检查及血脂、心电图、心血管超声等检查。运用聚合酶链式反应(polymerase chain reaction,PCR)扩增部分成员LDL-R基因启动子和18个外显子,测序后与GenBank中正常基因比对,确认是否存在突变。同时检测ApoB100基因,除外家族性载脂蛋白B100缺陷症(familial defective apolipoprotein B,FDB)。结果:共调查该家系3代8人。先证者父母为近亲结婚。其中7人诊断为FH患者,血清总胆固醇分别为18.98、8.69、7.51、7.36、11.64、9.24、9.57mmol/L(正常值:2.80~5.20mmol/L),临床诊断先证者为FH纯合子型,其余成员均为FH杂合子型。DNA测序排除该家系ApoB100基因突变,而先证者LDL-R基因第2号外显子第97位编码碱基存在碱基置换(CT),导致终止密码子在第12位提前出现,发生Q12X突变改变,基因型为TT纯合子;其父亲、母亲及胞弟均为携带Q12X突变的杂合子。结论:1.先证者及其胞弟、父、母、祖母、外祖母、二叔临床表现、体格检查、血脂测定及超声检查均支持FH诊断,且先证者已达到临床诊断FH纯合子标准,多数成员存在不同程度的动脉硬化;2.该家系ApoB100基因无突变,排除FDB的可能;3.先证者及其父母、胞弟LDL-R基因均存在Q12X突变,为终止突变,为该FH家系发病的分子基础;4.FH临床表现各不相同,受基因和环境因素共同作用。
[Abstract]:Objective: to investigate the molecular pathological mechanism of familial hypercholesterolemia (FH) and to analyze the relationship between gene mutation site and clinical phenotype in FH patients. Electrocardiogram, cardiovascular ultrasound and so on. The promoter and 18 exons of LDL-R gene were amplified by polymerase chain reaction polymerase chain reaction (PCR). After sequencing, they were compared with the normal gene in GenBank to confirm the existence of mutation. At the same time, the ApoB100 gene was detected. Results: a total of 3 generations of 8 people from this family were investigated. The proband parents were married to their close relatives. Seven of them were diagnosed as FH patients. The serum total cholesterol was 18.988 / 8.69 / 7.51 / 7.36 / 11.64 / 9.24 / 9.57 mmol / L (normal value: 2.80 / 5.20 mmol / L). The proband of clinical diagnosis was FH homozygous type, and the other members were FH heterozygote type. DNA sequencing excluded the mutation of ApoB100 gene in this family. The nucleotide substitution of the nucleotide sequence at 97 of exon 2 of the LDL-R gene in the proband led to the early emergence of the termination codon at the 12th position and the mutation of Q12X. The genotype was TT homozygote. Both mother and brother were heterozygous with Q12X mutation. Conclusion: 1. The proband and his brother, father, mother, grandmother, grandmother, second uncle clinical manifestation, physical examination, blood lipids test and ultrasonic examination all support the diagnosis of FH. Moreover, the proband had reached the standard of clinical diagnosis of FH homozygote, and most of the members had different degrees of arteriosclerosis 2.There was no mutation in the ApoB100 gene of this pedigree and the possibility of excluding FDB was excluded. The proband and his parents and siblings had Q12X mutation in the LDL-R gene, which was a termination mutation. 4. The clinical manifestations of FH were different and affected by gene and environmental factors.
【学位授予单位】：贵州医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R589.2
【参考文献】
中国期刊全文数据库 前10条
1 郭宇超;刘震宇;张抒扬;;家族性高胆固醇血症的药物治疗现状和进展[J];国际药学研究杂志;2017年02期
2 黄栎为;左明良;尹立雪;;超声诊断家族性高胆固醇血症患者主动脉瓣上狭窄矫治术后新发狭窄1例[J];中国超声医学杂志;2015年09期
3 范致星;杨超君;杨简;;PCSK9抑制剂Alirocumab降低LDL-C的研究新进展[J];海南医学;2015年15期
4 张筠婷;王绿娅;;家族性高胆固醇血症合并早发冠心病患者致病基因突变分析[J];中华实用诊断与治疗杂志;2015年06期
5 金文媛;赵正言;;低密度脂蛋白受体与代谢综合征的相关性研究进展[J];浙江大学学报(医学版);2015年01期
6 张志叶;张华;陈惠玲;;治疗纯合子型家族性高胆固醇血症新药米泊美生钠[J];中国新药杂志;2014年09期
7 王海红;王春梅;徐胜媛;孙立元;关啸;鲁昆;潘晓冬;刘飒;杨士伟;王绿娅;;1例家族性高胆固醇血症患者低密度脂蛋白受体基因新突变体功能研究[J];临床检验杂志;2014年05期
8 李春杏;靳松;朱珠;;家族性高胆固醇血症的药物治疗学概述[J];中国医院药学杂志;2014年05期
9 林e，
本文编号：1598916
本文链接：https://www.wllwen.com/yixuelunwen/nfm/1598916.html
最近更新
教材专著
