家族性高胆固醇血症低密度脂蛋白受体第13外显子突变分析  

Analysis of LDL receptor exon 13 mutation in patients with familial hypercholesterolemia

作　　者：孙立元[1] 潘晓冬[2] 苏鹏宇[2] 王旭[2] 代艳芳[2] 杨娅[3] 张小杉[3] 勇强[3] 杜兰平[2] 蔺洁[2] 赵景新[2] 王绿娅[2] 

机构地区：[1]首都医科大学附属北京安贞医院皮肤性病科,北京100029 [2]首都医科大学附属北京安贞医院-北京市心肺血管疾病研究所,北京100029 [3]首都医科大学附属北京安贞医院超声诊断科,北京100029

出　　处：《现代生物医学进展》2010年第13期2451-2454,2513,共5页Progress in Modern Biomedicine

基　　金：国家自然科学基金(30771986;30772356);北京市自然科学基金(7062010;7092016)项目资助

摘　　要：目的:探讨本课题组收集家族性高胆固醇血症(FH)患者中存在低密度脂蛋白受体(LDLR)第13外显子(E13)基因突变患者临床生化和心血管系统损害特点。方法:对9例临床诊断为FH、基因检测到LDLR基因E13突变的患者进行回顾性分析。结果:(1)临床诊断FH纯合子患者7名,其总胆固醇(TC)水平15.12～26.14mmol/L,杂合子患者2名,TC水平11.30～11.75mmol/L。(2)均可见不同程度黄色瘤;(3)FH纯合子3例心电图出现ST-T改变;4例儿童和1例青年患者出现瓣膜损害,冠脉血流储备(CVFR)减低;杂合子心电图检查均正常,1例出现瓣膜损害,CVFR均正常。(4)核苷酸序列分析证实:9例E13突变患者中,A606T纯合突变3名;D601Y纯合突变2名;A606T+W462X和A606T+D601Y复合杂合突变各1名;A606T和D601Y杂合突变各1名。结论:FH严重损害患儿心血管系统和皮肤,LDLR基因E13出现的A606T和D601Y突变可能成为中国FH人群的高频突变位点。Objective：To screen the mutation of LDLR gene exon 13 of which could be diagnosed as familial hypercholesterolemia（FH）,explore the relationship between the genotype and phenotype,and discuss the molecular pathologic mechanism.Methods：we retrospectively reviewed 9 patients who were agreed with clinical diagnostic criteria,and confirmed as LDLR exon13 mutations by gene screen.Results：（1） The level of cholesterol of FH homozygotes were very high（15.12～26.14 mmol/L） and heterozygotes were higher than normal（11.30～11.75 mmol/L）.（2） The lesions of xanthoma were found in all patients.（3） ST-T change were found in 3 homozygotes but not heterozygotes.Cardiac valve lesions and CFVR were found in 4 homozygotes and 1 heterozygotes by echocardiography.（3） No Mutations R3500Q of apoB100 were observed.（4） The homozygous mutations in exon13 of the LDLR gene（A606T and D601Y） were identified in 3 and 2 patients respectively,compound heterozygous mutations of A606T＋ W462X（E10） and A606T ＋ D601Y were identified in 2 patients and heterozygous mutations of A606T and D601Y were identified in 2 patients.Conclusion：The mutation in exon13 of the LDLR gene（A606T and D601Y） might predominate in the Chinese main land population.

关 键 词：高胆固醇血症 家族性 低密度脂蛋白受体 聚合酶链反应-单链构象多态性 突变 

分 类 号：R541.4[医药卫生—心血管疾病] Q493[医药卫生—内科学]