中文摘要：

目的对1例临床确诊为家族性高胆固醇血症（FH）、具有典型FH表型特征的患者进行载脂蛋白B100（apoB100）基因、低密度脂蛋白受体（LDLR）基因分析,探讨患者发病机制,分析基因型与临床表型间的关系。方法常规血脂测定,提取患者及其父母基因组DNA,扩增apoB100基因第26号外显子蛋白编码3500区域及LDLR基因全部18个外显子,对扩增目的片段进行核苷酸测序,结果与GenBank比对分析。结果患者血清TC 16.8 mmol/L,LDL-C 13.1 mmol/L,apoB100基因第26外显子10707位核苷酸C改变为T,导致apoB100基因3500位上精氨酸被色氨酸置换,为R3500W杂合突变;LDLR基因中第13外显子1879位核苷酸G改变为A,导致丙氨酸被苏氨酸置换,为A606T杂合突变。患者父亲存在与患者一致的apoB100基因R3500W杂合突变,母亲存在与患者一致的LDLR基因A606T杂合突变。结论患者的2个突变基因分别遗传自父母,基因突变导致患者同时发生apoB100缺陷症（FDB）及FH,是FDB/FH双基因复合杂合子,患者有严重的FH表型,临床确诊为纯合FH。

英文摘要：

Objective To investigate the mutation of ApoB100 gene and LDL-R gene in a patient with familial hypercholesterolemia（FH）.Methods The proband and her parents′ blood samples were taken after a 12-h fast for lipid clinical exams,and genomic DNA was isolated.In codon 3500 region,the exon 26 of ApoB100 gene,promoter region and 18 exons of the LDL-R gene were amplified by PCR and sequenced.Results The serum total cholesterol level of the patient was 16.8 mmol/L.A single base substitution（C for T） in exon 26 changed codon 3500 in the mature protein from arginine to tryptophan（R3500W）.The other mutant allele had a single base pair substitution of G for A in the codon for residue 1879 in exon 13,which introduced the change from alanine to threonine（A606T）.The proband′s father and mother showed R3500W and A606T mutations respectively.Conclusions The mutations of R3500W in ApoB100 gene and A606T in LDL-R gene,which were inherited from the patient′s father and mother,are associated with HF.The proband has homozygous phenotype although genotype analysis indicates FH/FDB compound heterozygote mutations.