2代3人同患家族性高胆固醇血症及其低密度脂蛋白受体基因突变分析

目的　调查姐妹二人同患家族性高胆固醇血症的家系并进行系谱分析。方法　根据患者及其家系的血缘关系绘制家系图谱，分析临床症状和血脂检查资料。结果　先证者女性，17岁,血清胆固醇浓度为18.89 mmol/L，3岁时即有臀部黄色瘤, 17岁时首次发生前壁心肌梗死，其姐血清胆固醇浓度为15.23 mmol/L，全身多处黄脂瘤。初步诊断先证者为纯合子型，其姐为杂合型。检查患儿4代29人,根据血脂和临床表现确诊2例杂子型家族性高胆固醇血症患者,系谱分析该家系遗传方式符合常染色体显性遗传规律。结论　初步证实一个纯合子型家族性高胆固醇血症系谱。

Mutation analysis of low-density lipoprotein receptor gene in3 patients with familial hypercholesterolemia in two generations

Objective To investigate the mutation of low-density lipoprotein receptor(LDL-R) gene in 3 patients with familial hypercholesterolemia(FH) in two generations,so as to discuss the pathogenesis of FH.Methods A 17-year-old patients was selected to undergo physical examination,lipid level test,electrocardiography,cardiac ultrasound and coronary artery angiography.Pedigree analysis was carried out based on family investigation.The promoter and the 18 exons of the LDL-R gene and the flank sequence were amplified by PCR;DNA sequencing was used to detect point mutation.Ninety normal subjects from the native place of the proband and 190 subjects from random population were taken as controls.Results Totally 28 members of 4 generations were examined.The proband,her elder sister and grandaunt had FH with xanthoma,and their total cholesterol(TC) levels were 18.89 mmol/L,15.23 mmol/L,and 12.89 mmol/L,respectively.Pedigree analysis showed that the genetic pattern of this family was consistent to autosomal dominant inheritance trait.DNA sequencing demonstrated that a G1448A substitution caused a nonsense mutation TGG to TAG in exon 10 of LDL-R gene,a Trp→462 stop mutation.The mutation of the proband,her older sister and grandaunt were homozygous,heterozygous and heterozygous,respectively.The same mutation was not detected in the family members from the proband’s father and people from control group.Conclusion The proband,her elder sister and grandaunt have the same mutation,the Trp→462 stop mutation in exon 10 of LDL-R gene,which might be the key mutation that causes FH in this pedigree.