家族性高胆固醇血症一家系临床表现及其低密度脂蛋白受体基因突变分析

发布时间：2018-02-28 03:51

本文关键词： 家族性高胆固醇血症低密度脂蛋白受体基因突变　出处：《中国皮肤性病学杂志》2017年06期 　论文类型：期刊论文

【摘要】：目的探讨家族性高胆固醇血症(FH)患者低密度脂蛋白受体(LDL-R)基因突变与临床表型之间的关系。方法以FH先证者及其家系为研究对象,绘制家系图谱,对其成员进行常规体格检查、血脂测定、心电图、心血管超声等检查。以PCR法分别扩增启动子和全部18个外显子片段,产物经电泳鉴定后直接测序分析。同时PCR扩增ApoB100基因包含R3500Q,R3501W,R3531C和R3480W位点的序列,产物电泳鉴定后测序,以排除家族性载脂蛋白B100缺陷症(FDB)。结果共调查3代8人,先证者父母为姨表近亲结婚。家系中共有FH患者7例,7人血清总胆固醇均升高,临床诊断先证者为纯合子型,余均为杂合子型。系谱分析该家族遗传方式符合常染色体显性遗传规律。DNA测序排除该家系ApoB100基因R3500Q,R3501W,R3531C和R3480W位点突变,而先证者LDLR基因第2号外显子第97位编码碱基存在碱基置换(C→T),导致终止密码子在第12位提前出现,发生Q12X突变改变,基因型为TT纯合子;其父亲、母亲及胞弟均为携带Q12X突变的杂合子。结论先证者及其父母、胞弟LDL-R基因均存在Q12X突变,为终止突变,此位点的突变可能是该家系发病的分子基础。
[Abstract]:Objective to investigate the relationship between the low density lipoprotein receptor (LDL-R) gene mutation and clinical phenotype in patients with familial hypercholesterolemia / FHemia. The promoter and all 18 exon fragments were amplified by PCR method. The products were identified by electrophoresis and sequenced directly. Meanwhile, the ApoB100 gene was amplified by PCR containing R3500QN R3501WN R3531C and R3480W loci. The products were identified by electrophoretic analysis and sequenced to exclude familial apolipoprotein B100 deficiency (FDB100). Results A total of 3 generations of 8 patients were investigated, and the proband parents were related to their cousins. The serum total cholesterol levels of 7 patients with FH were all increased. The proband of clinical diagnosis was homozygous and heterozygous. The genetic pattern of the family was in accordance with the autosomal dominant inheritance pattern. DNA sequencing excluded the mutation of R3500QN R3501WN R3531C and R3480W loci in the family. The nucleotide substitution was found in the 97th coding base of exon 2 of the LDLR gene in the proband. 鈫扖onclusion Q12X mutation is present in the LDL-R gene of the proband and their parents, and the genotype is TT homozygous, and the father, mother and brother are all heterozygotes with Q12X mutation. In order to stop the mutation, the mutation at this site may be the molecular basis of the family.
【作者单位】：贵州医科大学附属医院皮肤科;贵州医科大学第二附属医院皮肤科;河南省第二人民医院皮肤科;
【基金】：贵州省科技合作计划项目(黔科合LH字[2015]7369)
【分类号】：R589.2

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