家族性高胆固醇血症黄色瘤的家系遗传分析  

Genetic analysis in the patients with familial hypercholesterolemia

作　　者：周瑜琳[1] 赵咏桔[1] 崔斌[1] 罗邦尧[1] 朱鋐达[1] 顾雪疆[1] 李小英[1] 宁光[1] 

机构地区：[1]上海第二医科大学附属瑞金医院内分泌代谢科,上海200025

出　　处：《诊断学理论与实践》2005年第6期473-476,共4页Journal of Diagnostics Concepts & Practice

摘　　要：目的:检测中国汉族家族性高胆固醇血症(familial hyper-cholesterolemia,FH)家系低密度脂蛋白受体(LDLR)基因突变,探讨FH发病的分子机制。方法:采用PCR扩增结合核苷酸序列分析检测1例临床诊断为FH纯合子患者及其家系成员LDLR基因启动子和全部18个外显子片段,结果与GenBank公布的该基因正常序列对比找出突变,同时检测载脂蛋白B100(apoB100)基因Q3500R突变,以排除家族性apoB100缺陷症。结果:该患者LDLR基因第12外显子的第1747位和1773位碱基发生替换,前者导致H583Y突变,而后者未发现氨基酸改变。同时未检测出患者及其核心家系成员apoB100Q3500R突变。结论:FH是一常染色体显性遗传性疾病,为基因突变导致LDLR缺陷所致的遗传性疾病。检测相关基因突变对临床干预和遗传指导有参考价值。Objective To investigate the low density lipoprotein receptor （LDLR） gene mutation in a Lhlnese tamlly with familial hypercholesterolemia （FH） and discuss the molecular pathological mechanism. Methods The screening was carried out using touch-down PCR and agarose gel electrophoresis in combination with DNA sequence analysis. The resuits were compared with the normal sequences in GenBank to find the mutation. In addition, the apolipoprotein B100 （apoB100） gene for known mutations （R3500Q） that cause familial defective apoB100 （FDB） was detected. Results Two substitutions at 1 747 and 1 773 bp of exon 12 were found in the proband. The former introduced a H583Y mutation and the latter was a nonsense one. No R3500Q mutations of apoB100 were observed. Conclusions FH is an euchromosome dominant genetic disease that is caused by the defective LDLR resulted from gene mutation. The detection of the relative gene mutation is valuable for the clinical and genetic works.

关 键 词：家族性高胆固醇血症 低密度脂蛋白受体 基因突变 

分 类 号：R596.1[医药卫生—内科学] R739.5[医药卫生—临床医学]