Inbal A, Seligsohn U, Kornbrot N, Brenner B, Harrison P, Randi A, Rabinowitz I, Sadler J E
Hematology Unit, Beilinson Medical Center, Israel.
Thromb Haemost. 1992 Jun 1;67(6):618-22.
Von Willebrand disease (vWD) type IIA is characterized by decreased ristocetin-induced platelet aggregation, and by the absence from plasma of high molecular weight multimers of von Willebrand factor (vWF). Most mutations causing vWD type IIA are clustered within the A2 domain of the mature vWF subunit that is encoded by exon 28. Using the polymerase chain reaction (PCR), the entire exon 28 from patients with vWD type IIA and normal controls was amplified and sequenced. Three missense mutations were detected that result in the amino acid substitutions were detected that result in the amino acid substitutions Arg(834)----Trp, Gly(742)----Glu, and Ser(743)----Leu. The first mutation occurred independently in three unrelated families; each of the latter mutations was found in one family. By restriction endonuclease analysis and allele-specific oligonucleotide (ASO) hybridization the mutations were confirmed in affected family members and excluded in unaffected members and 50 normal controls. The apparently high frequency of identical independent mutations among patients with vWD type IIA suggests that a precise diagnosis may be possible in a majority of patients using relatively simple recombinant DNA screening assays.
IIA型血管性血友病（vWD）的特征是瑞斯托菌素诱导的血小板聚集减少，且血浆中缺乏高分子量的血管性血友病因子（vWF）多聚体。导致IIA型vWD的大多数突变集中在由外显子28编码的成熟vWF亚基的A2结构域内。使用聚合酶链反应（PCR）对IIA型vWD患者和正常对照的整个外显子28进行扩增和测序。检测到三个错义突变，这些突变导致了氨基酸替换，分别为Arg(834)→Trp、Gly(742)→Glu和Ser(743)→Leu。第一个突变在三个不相关的家族中独立出现；后两个突变分别在一个家族中被发现。通过限制性内切酶分析和等位基因特异性寡核苷酸（ASO）杂交，在受影响的家族成员中证实了这些突变，并在未受影响的成员和50名正常对照中排除了这些突变。IIA型vWD患者中相同独立突变的明显高频率表明，使用相对简单的重组DNA筛查试验，大多数患者可能可以进行精确诊断。
