Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease characterized by high levels of low-density lipoprotein-cholesterol (LDLc), associated to premature cardiovascular disease. The detection of the variants related to FH is important to improve the early diagnosis in probands / index-cases (ICs) and their relatives. We included ICs with FH and their relatives, living in a small region of Minas Gerais state-Brazil, which were classified according to Dutch Lipid Clinic Network Criteria (DLCNC) and submitted to sequencing of genes related to FH (LDLR, APOB, PCSK9, LDLRAP1, LIPA, STAP1, APOE, ABCG5 e ABCG8). In a total of 143 subjects (32 ICs and 111 relatives), eight variants were identified in 91 individuals. From these variants, five were in LDLR [p.(Asp224Asn), p.(Ser854Gly), p.(Cys34Arg), p.(Asp601His), deletion of exon15 in LDLR)], one in APOB [p.(Met499Val)], one in PCSK9 [p.(Arg237Trp)] and one in APOE [p.(Pro28Leu)] genes. The variants were detected in 100% of those subjects classified as definitive, 87% as probable and 69% as possible FH cases based on DLCNC. The LDLc level was higher in individuals with corneal arch and xanthomas or xanthelasmas, as well as in pathogenic or probably pathogenic variants carriers. This study showed higher frequency of LDLR gene variants compared to other genes related to LDL metabolism in individuals with FH in Minas Gerais – Brazil and the presence of FH in relatives without previous diagnosis. Our data reinforce the importance of molecular and clinical evaluation of FH relatives in order to early diagnosis the FH, as well as cardiovascular diseases prevention.

家族性高胆固醇血症（FH）是常染色体显性遗传病，其特征是高水平的低密度脂蛋白胆固醇（LDLc）与心血管疾病有关。与FH相关的变体的检测对于改善先证者/索引病例（IC）及其亲属的早期诊断非常重要。我们纳入了具有FH及其亲属的IC，它们生活在巴西米纳斯吉拉斯州的一个小地区，并根据荷兰脂质临床网络标准（DLCNC）进行了分类，并提交了与FH相关的基因测序（LDLR，APOB，PCSK9，LDLRAP1，LIPA，STAP1，APOE，ABCG5 eABCG8）。在总共143个受试者（32个IC和111个亲属）中，在91个个体中鉴定出8个变异体。在这些变体中，LDLR中有五种[p。（Asp224Asn），p。（Ser854Gly），p。（Cys34Arg），p。（Asp601His），LDLR中exon15的缺失），APOB中的一种[p。（Met499Val） ]，一个在PCSK9 [p。（Arg237Trp）]基因中，另一个在APOE [p。（Pro28Leu）]基因中。在基于DLCNC的FH病例中，有100％被归为确定性，87％为可能和69％的FH患者中检测到了变异。LDLc水平在患有角膜弓和黄瘤或黄瘤的个体以及致病或可能致病的变异携带者中较高。这项研究表明LDLR的频率更高与巴西米纳斯吉拉斯州患有FH的人的LDL代谢相关基因相比，该基因变异与其他基因有关，并且在没有事先诊断的亲属中存在FH。我们的数据强调了对FH亲属进行分子和临床评估的重要性，以便及早诊断FH以及预防心血管疾病。