Salazar Luis A, Hirata Mario H, Cavalli Selma A, Nakandakare Edna R, Forti Neusa, Diament Jaime, Giannini Sérgio D, Bertolami Marcelo C, Hirata Rosario D C
Faculty of Pharmaceutical Sciences Medical School, University of Sao Paulo, Sao Paulo, SP, Brazil.
Hum Mutat. 2002 Apr;19(4):462-3. doi: 10.1002/humu.9032.
Low-density lipoprotein receptor (LDLR) gene mutations cause familial hypercholesterol-emia (FH), one of the most common single gene disorders. The spectrum of LDLR mutations in Brazil is not known. The aim of this study was the characterization of LDLR mutations in 35 unrelated Brazilian patients with heterozygous FH. The promoter region, the 18 exons and the flanking intron sequences of the LDLR gene were screened by PCR-SSCP analysis and by DNA sequencing. In addition, we have screened the apolipoprotein B gene (APOB) for known mutations (R3500Q and R3531C) that cause Familial defective apo B-100 (FDB) by PCR-RFLP procedure. We found two nonsense (E92X and C371X) and six missense LDLR mutations (R236W, G322S, G352D, A370T, C675W and C677Y), that were previously described in FH patients from other populations. We also found five novel missense [G(-20)R, T476P, V503G, D580H and S652R] and two novel frame shift LDLR mutations (FsR757 and FsS828). Four patients were found to carry two different mutations in the LDLR gene: G352D and A370T (one patient), S652R and C675W (one patient) and T476P and V503G (two patients). APOB mutations were not found. These findings demonstrate that there is a broad spectrum of mutations in the LDLR gene in FH individuals from Brazil.
低密度脂蛋白受体（LDLR）基因突变会导致家族性高胆固醇血症（FH），这是最常见的单基因疾病之一。巴西LDLR突变的情况尚不清楚。本研究的目的是对35名不相关的巴西杂合子FH患者的LDLR突变进行特征分析。通过PCR-SSCP分析和DNA测序对LDLR基因的启动子区域、18个外显子及其侧翼内含子序列进行筛查。此外，我们还通过PCR-RFLP方法对载脂蛋白B基因（APOB）进行已知突变（R3500Q和R3531C）的筛查，这些突变会导致家族性缺陷载脂蛋白B-100（FDB）。我们发现了两个无义突变（E92X和C371X）和六个错义LDLR突变（R236W、G322S、G352D、A370T、C675W和C677Y），这些突变先前在其他人群的FH患者中已有描述。我们还发现了五个新的错义突变[G(-20)R、T476P、V503G、D580H和S652R]和两个新的移码LDLR突变（FsR757和FsS828）。发现四名患者在LDLR基因中携带两种不同的突变：G352D和A370T（一名患者）、S652R和C675W（一名患者）以及T476P和V503G（两名患者）。未发现APOB突变。这些发现表明，巴西FH个体的LDLR基因存在广泛的突变谱。
