一个家族性高胆固醇血症家系基因突变分析  

The analysis of gene mutationa in a familial hypercholesterolemia family

作　　者：张筠婷[1] 郑金刚[1] 柯元南[1] 王绿娅[2] 

机构地区：[1]中日友好医院心内科,北京100029 [2]北京安贞医院心肺血管疾病研究所,北京100029

出　　处：《中日友好医院学报》2015年第2期80-83,F0003,共5页Journal of China-Japan Friendship Hospital

基　　金：国家自然科学基金(81170810;81471098);北京市自然科学基金(7112022)

摘　　要：目的:对临床确诊的一个家族性高胆固醇血症(FH)纯合子家系进行基因突变分析,分析基因型与临床表型之间的关系,探讨其发病机制。方法:在这个包括48名成员的家系中,16例患者有高胆固醇血症。提取患者及家系成员外周血基因组DNA,对患者聚合酶链反应扩增ApoB100基因Q3500R位点并进行测序,确定有无常见突变,同时对包括患者在内的48名成员针对与PCSK9基因相连锁的微卫星位点D1S417,D1S2797,D1S2890以及与LDL-R基因相连锁的微卫星位点D19S221,D19S394进行连锁分析。结果 :核苷酸序列分析未发现ApoB100基因Q3500R突变,数个常见的与LDL-R基因或PCSK9基因相连锁的微卫星多态位点与此FH无连锁。结论:对该FH家系,未发现常见的ApoB100突变,微卫星多态性分析未发现与LDL-R基因,PCSK9基因连锁的多态性存在。是否存在新的突变基因,尚需下一步通过全基因组扫描验证。Objective：To analysis the gene mutation of the clinial diagnosis of a homozygous familial hypercholesterolemia family and explore the relationship between the genotype and the phenotype,investigate its pathogenesis.Methods：The family had 48 members,including 16 patients with hypercholesterolemia.We extracted genomic DNA of peripheral blood in patients and the family members, and amplified Apo B100Q3500 R gene fragments by polymerase chain reaction to determine whether there existed the common mutations.At the same time,using linkage analysis for all the family members including the proband by Microsatellite loci D1S417,D1S2797,D1S2890 linked with PCSK9 gene and Microsatellite loci D19S221,D19S394 linked with LDL-R gene.Results：Nucleotide sequence analysis of mutations were not found in Apo B100Q3500 R gene.Common polymorphic microsatellite loci which linkaged with LDL-R gene and PCSK9 gene had no linkage with the familial hypercholesterolemia family.Conclusion：There was no common mutation in Apo B100 gene using sequencing method,Microsatellite analysis found no linkage with LDL-R gene and PCSK9 gene.It still need the next verification by whole genome scanning to determine whether exsist a new pathogenic gene.

关 键 词：家族性高胆固醇血症 低密度脂蛋白受体 基因突变 PCSK9 

分 类 号：R589.2[医药卫生—内分泌]