Minnich A, Roy M, Chamberland A, Lavigne J, Davignon J
Department of Hyperlipidemia and Atherosclerosis, Clinical Research Institute of Montreal, P.Q. Canada.
Clin Biochem. 1995 Jun;28(3):277-84. doi: 10.1016/0009-9120(94)00072-4.
Due to a genetic founder effect, five mutations in the low-density lipoprotein receptor gene account for approximately 83% of familial hypercholesterolemia (FH) diagnosed in French-Canadians. The most frequent mutation, present in 61% of heterozygotes, is a > 10 kb deletion of the 5' region of the gene that removes the promoter and the first exon, resulting in a null allele. Other less prevalent mutations include a gene deletion of approximately 5 kb, which removes exons 2 and 3 (2% of cases) and three missense mutations: Trp66-->Gly (exon 3) (12%), Glu207-->Lys (exon 4) (3%), and Cys646-->Tyr (exon 14) (6%). The apoB Arg3500-->Gln mutation was absent in 228 French Canadians with the FH phenotype. Taking advantage of the availability of fluorescent DNA detection, we have substantially improved the assays for these mutations.
由于遗传奠基者效应，低密度脂蛋白受体基因中的五个突变约占在法裔加拿大人中诊断出的家族性高胆固醇血症（FH）的83%。最常见的突变存在于61%的杂合子中，是该基因5'区域大于10 kb的缺失，其去除了启动子和第一个外显子，导致无效等位基因。其他不太常见的突变包括约5 kb的基因缺失，其去除了外显子2和3（2%的病例）以及三个错义突变：Trp66→Gly（外显子3）（12%）、Glu207→Lys（外显子4）（3%）和Cys646→Tyr（外显子14）（6%）。在228名具有FH表型的法裔加拿大人中未发现载脂蛋白B Arg3500→Gln突变。利用荧光DNA检测的可行性，我们已大幅改进了这些突变的检测方法。
