目的调查2代3人同患家族性高胆固醇血症(familial hypercholesterolemia,FH)的家系,并检测和分析低密度脂蛋白受体(LDL-R)基因突变,以探讨FH发病的分子机制。方法对17岁先证者进行体格、心电图、血脂水平、心脏超声、冠状动脉造影检查。根据患者及其家系的血缘关系绘制家系图谱。以PCR法分别扩增家系成员LDL-R基因启动子、18个外显子及侧翼序列,应用直接测序法进行突变检测;并以90名来自患者原籍的正常人群和190个随机人群样本为对照。结果共检查先证者4代28人。先证者、其胞姐及姨外祖母均为FH黄色瘤患者,3人血浆总胆固醇分别为18.89、15.23、12.89mmol/L;临床诊断基因型分别为纯合型、杂合型及杂合型。系谱分析该家系遗传方式符合常染色体显性遗传规律。核苷酸序列分析显示3名患者LDL-R基因的10号外显子存在G1448A改变,为W462X终止突变。先证者、其胞姐及姨外祖母的基因型分别是GA、GA、AA;先证者的父亲家系均为GG纯合子。90名来自患者原籍的正常人群和190个随机人群样本该位点测序结果均为GG纯合子。结论3名患者LDL-R基因均存在G1448A突变,为终止突变,来自母系亲属,此位点的突变很可能是该家系发病的分子基础。 Objective To investigate the relationship between familial hypercholesterolemia (FH) and familial hyperplasia (FH) in two generations of three generations and to detect and analyze the mutation of low density lipoprotein receptor (LDL-R) gene in order to explore the molecular mechanism of FH pathogenesis. Methods The 17-year-old probands were examined by physical examination, electrocardiogram, blood lipid, echocardiography and coronary angiography. Draw a pedigree based on the blood relationship of patients and their families. The promoter, 18 exons and flanking sequences of LDL-R gene were amplified by polymerase chain reaction (PCR), respectively. The mutations were detected by direct sequencing. 90 samples of normal population from 190 patients and 190 random samples were used as controls . Results A total of 28 probands were examined for 4 generations. The proband, his sister and aunt grandmother were FH yellow tumor patients, 3 plasma total cholesterol were 18.89,15.23,12.89mmol / L; clinical diagnosis of genotypes were homozygous, heterozygous and heterozygous . Pedigree analysis of the pedigree’s genetic patterns consistent with autosomal dominant inheritance. Nucleotide sequence analysis showed that there was G1448A change in exon 10 of LDL-R gene in 3 patients, which was the termination mutation of W462X. The probands, their sister and aunt grandmother genotypes were GA, GA, AA; proband’s father’s family are GG homozygotes. 90 samples from normal population of patients originating from 190 random populations were sequenced as GG homozygotes. Conclusions There are G1448A mutation in LDL-R gene in all 3 patients, which is the termination mutation from maternal relatives. The mutation in this locus may be the molecular basis of the disease.