Schuster H, Stiefenhofer B, Wolfram G, Keller C, Humphries S, Huber A, Zöllner N
Medizinische Poliklinik Universität, München, Federal Republic of Germany.
Hum Genet. 1989 Apr;82(1):69-72. doi: 10.1007/BF00288276.
To examine the potential usefulness of restriction fragment length polymorphisms (RFLPs) for diagnosis of familial hypercholesterolemia (FH), we determined the genotype of FH patients and their relatives for the Apa1I, NcoI, PvuII and StuI RFLP of the LDL-receptor gene in a sample of German patients attending the Lipid Clinic in Munich. There was no significant difference in the relative allele frequency between the group of FH patients and controls for any of the four polymorphisms. Using linkage analysis, we could determine the four-RFLP haplotypes of 39 defective and 90 normal LDL-receptor genes in 38 FH families. In our sample, defective LDL-receptor genes occur on 6 different chromosomes determined by the four RFLPs. This suggests that at least 6 different genetic defects may cause FH in this sample. RFLPs of the LDL-receptor gene cannot be used to detect FH in individuals; however, appropriate diagnosis can be carried out in more than 90% of families using linkage analysis and these RFLPs.
为了研究限制性片段长度多态性（RFLP）在家族性高胆固醇血症（FH）诊断中的潜在用途，我们在慕尼黑脂质诊所就诊的德国患者样本中，确定了FH患者及其亲属低密度脂蛋白受体基因的Apa1I、NcoI、PvuII和StuI RFLP的基因型。在这四种多态性中，FH患者组和对照组之间的相对等位基因频率没有显著差异。通过连锁分析，我们能够确定38个FH家族中39个缺陷型和90个正常低密度脂蛋白受体基因的四RFLP单倍型。在我们的样本中，由这四种RFLP确定的缺陷型低密度脂蛋白受体基因出现在6条不同的染色体上。这表明在这个样本中至少有6种不同的基因缺陷可能导致FH。低密度脂蛋白受体基因的RFLP不能用于检测个体中的FH；然而，使用连锁分析和这些RFLP可以在90%以上的家族中进行准确诊断。
