Verweij C L, Quadt R, Briët E, Dubbeldam K, van Ommen G B, Pannekoek H
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Department of Molecular Biology, Amsterdam, The Netherlands.
J Clin Invest. 1988 Apr;81(4):1116-21. doi: 10.1172/JCI113425.
Restriction fragment length polymorphisms (RFLPs), using the enzymes Bgl II and Xba I in conjunction with human von Willebrand factor (vWF) cDNA probes, have been described previously. In the present study we demonstrate the localization of both genetic markers within the vWF gene. The RFLPs were used to study the segregation of alleles associated with von Willebrand's disease (vWD) type IIA in a comprehensive, affected family. Individuals of this family were tested for their bleeding time and their plasma was analyzed for vWF antigen concentration and vWF ristocetin-cofactor activity. Based on these data, the affected members were diagnosed as vWD type-IIA patients; this conclusion was confirmed by the analysis of the multimeric vWF pattern of some of the patients. It was demonstrated that both RFLPs are completely linked with the vWD type-IIA trait. From this finding, we conclude that the defect that causes the vWD type IIA is most likely due to a mutation in the vWF gene and not to a mutation in a gene involved in posttranslational processing of the vWF protein.
先前已描述了使用Bgl II和Xba I酶结合人血管性血友病因子（vWF）cDNA探针的限制性片段长度多态性（RFLP）。在本研究中，我们展示了这两种遗传标记在vWF基因内的定位。这些RFLP被用于研究一个全面的、受影响家庭中与IIA型血管性血友病（vWD）相关的等位基因的分离情况。对这个家庭的个体进行出血时间检测，并分析其血浆中的vWF抗原浓度和vWF瑞斯托霉素辅因子活性。基于这些数据，受影响的成员被诊断为IIA型vWD患者；通过对部分患者的多聚体vWF模式分析，这一结论得到了证实。结果表明，这两种RFLP都与IIA型vWD性状完全连锁。从这一发现中，我们得出结论，导致IIA型vWD的缺陷很可能是由于vWF基因中的突变，而不是由于参与vWF蛋白翻译后加工的基因中的突变。
