中文摘要：

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。

英文摘要：

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.