Ma Y H, Bétard C, Roy M, Davignon J, Kessling A M
Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montréal, Québec, Canada.
Clin Genet. 1989 Oct;36(4):219-28. doi: 10.1111/j.1399-0004.1989.tb03194.x.
Hobbs et al. (N. Engl. J. Med. 317: 734-737, 1987) reported a large deletion of approximately 10 kilobases in the 5' portion of the human low-density lipoprotein (LDL) receptor gene. This deletion affects about 60% of familial hypercholesterolemia (FH) heterozygotes in the French Canadian population. We have developed a rapid, convenient method for the detection of the deletion using double digestion with the restriction enzymes XbaI and EcoRV, or triple digestion with XbaI, EcoRV and XmnI, and a 650 bp cDNA probe, radio-labeled using a random oligonucleotide primer technique. Eighty French Canadian FH heterozygotes were screened for the presence of the deletion. Forty-seven (59%) of them were found to carry the 10 kb deletion. Using the same method, we also identified a new mutation which was found in four of the 80 (5%) FH patients. This mutation has been found to be a 5 kb deletion removing exons 2 and 3 of the LDL receptor gene, which correspond to the first two repeats of the LDL receptor binding domain. Cosegregation of the 5 kb deletion and the FH phenotype was observed in one family. Possible structure-function relationship is discussed.
霍布斯等人（《新英格兰医学杂志》317: 734 - 737, 1987）报道，人类低密度脂蛋白（LDL）受体基因5'端部分存在约10千碱基的大片段缺失。这种缺失影响了法裔加拿大人群中约60%的家族性高胆固醇血症（FH）杂合子。我们开发了一种快速、便捷的方法来检测这种缺失，即使用限制性内切酶XbaI和EcoRV进行双酶切，或使用XbaI、EcoRV和XmnI进行三酶切，并使用随机寡核苷酸引物技术进行放射性标记的650 bp cDNA探针。对80名法裔加拿大FH杂合子进行了缺失检测筛查。其中47名（59%）被发现携带10 kb的缺失。使用相同的方法，我们还鉴定出一种新的突变，在80名FH患者中有4名（5%）存在这种突变。已发现该突变是一个5 kb的缺失，去除了LDL受体基因的外显子2和3，这两个外显子对应于LDL受体结合域的前两个重复序列。在一个家族中观察到5 kb缺失与FH表型的共分离。讨论了可能的结构 - 功能关系。
