Donnér M, Kristoffersson A C, Berntorp E, Scheibel E, Thorsen S, Dahlbäck B, Nilsson I M, Holmberg L
Dept of Paediatrics, University Hospital, Lund, Sweden.
Eur J Haematol. 1993 Jul;51(1):38-44.
Recently, several von Willebrand factor gene mutations resulting in type IIA von Willebrand's disease have been reported. We examined 8 patients from Sweden and Denmark with this phenotype and found two new candidate mutations and a hitherto unknown amino acid polymorphism. One patient had a de novo occurring mutation resulting in substitution of glycine for arginine 834. Previous reports have demonstrated conversion of arginine 834 to tryptophan or glutamine in IIA patients. A 2nd patient had a G(4825)-->A transition, substituting arginine for glycine 846. The transition produces a sequence congruent with that of the pseudogene but several lines of evidence indicate that a sequencing error due to influence by the latter could be excluded. The remaining 6 patients had one of the earlier described substitution mutations: Ser743-->Leu and Ile865-->Thr. In addition, two sequence variations not linked to the phenotype were found, namely Tyr821-->Cys and Val802-->Leu.
最近，有报道称几种导致IIA型血管性血友病的血管性血友病因子基因突变。我们研究了来自瑞典和丹麦的8例具有该表型的患者，发现了两个新的候选突变和一个迄今未知的氨基酸多态性。一名患者发生了新生突变，导致第834位精氨酸被甘氨酸取代。先前的报道已证实在IIA型患者中第834位精氨酸可转变为色氨酸或谷氨酰胺。第二名患者发生了G(4825)-->A转换，第846位甘氨酸被精氨酸取代。该转换产生的序列与假基因的序列一致，但有几条证据表明可以排除因受后者影响而导致的测序错误。其余6例患者具有先前描述的替代突变之一：Ser743-->Leu和Ile865-->Thr。此外，还发现了两个与该表型无关的序列变异，即Tyr821-->Cys和Val802-->Leu。
