Molecular basis of human von Willebrand disease: analysis of platelet von Willebrand factor mRNA.
Molecular basis of human von Willebrand disease: analysis of platelet von Willebrand factor mRNA.
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人类血管性血友病的分子基础：血小板血管性血友病因子 mRNA 分析。
DOI：
10.1073/pnas.86.10.3723
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发表时间：
1989
影响因子：
11.1
通讯作者：
Yang,AY
中科院分区：
文献类型：
--
作者：
Ginsburg,D;Konkle,BA;Gill,JC;Montgomery,RR;Bockenstedt,PL;Johnson,TA;Yang,AY
血管性血友病（vWD）是人类最常见的遗传性出血性疾病，可由黏附糖蛋白血管性血友病因子（vWF）的定量或定性缺陷引起。vWF基因的大尺寸和难以从患者身上获得vWF mRNA，限制了vWD的分子研究。利用聚合酶链反应的适应性，从外周血血小板中扩增vWF mRNA并进行测序。发现了一个沉默的vWF等位基因，这是由vWF mRNA转录或加工的顺式缺陷引起的。在两例IIA型vWD患者中，发现了两个不同但相邻的错义突变，其位置可能确定了一个重要的vWF功能域。含有后一种突变的重组vWF在异源细胞中的表达再现了IIA型vWD血浆中所见的特征性结构异常。
von Willebrand disease (vWD), the most common inherited bleeding disorder in humans, can result from either a quantitative or a qualitative defect in the adhesive glycoprotein, von Willebrand factor (vWF). Molecular studies of vWD have been limited by the large size of the vWF gene and difficulty in obtaining the vWF mRNA from patients. By use of an adaptation of the polymerase chain reaction, vWF mRNA was amplified and sequenced from peripheral blood platelets. A silent vWF allele was identified, resulting from a cis defect in vWF mRNA transcription or processing. In two type IIA vWD patients, two different but adjacent missense mutations were identified, the locations of which may identify an important vWF functional domain. Expression in heterologous cells of recombinant vWF containing one of these latter mutations reproduced the characteristic structural abnormality seen in type IIA vWD plasma.