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Thromb Haemost 1992; 67(06): 612-617
DOI: 10.1055/s-0038-1648510
Original Articles
Schattauer GmbH Stuttgart

Three Distinct Candidate Point Mutations of the von Willebrand Factor Gene in Four Patients with Type IIA von Willebrand Disease

Isamu Sugiura
1   The First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan
,
Tadashi Matsushita
1   The First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan
,
Mitsune Tanimoto
1   The First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan
,
Isao Takahashi
1   The First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan
,
Tomio Yamazaki
1   The First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan
,
Koji Yamamoto
1   The First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan
,
Junki Takamatsu
1   The First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan
,
Tadashi Kamiya
2   Aichi Red Cross Blood Center, Seto, Japan
,
Hidehiko Saito
1   The First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan
3   Aichi Blood Disease Research Foundation, Nagoya, Japan
› Author Affiliations
Further Information

Publication History

Received 22 July 1991

Accepted after revision 08 January 1992

Publication Date:
03 July 2018 (online)

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Summary

Type IIA von Willebrand disease (vWD) is the most common type II vWD and is characterized by the selective loss of large and intermediate sized multimers. One explanation for this disorder has been postulated to be a qualitative defect in von Willebrand factor (vWF) which results in increased susceptibility to proteolysis at the bond between residues Tyr842 and Met843. Four missense mutations that may cause type IIA vWD have recently been identified near the cleavage site. We analyzed the molecular basis for type IIA vWD in six patients. A 512 bp DNA sequence spanning the proteolytic cleavage site was targeted for PCR amplification and sequencing. We exploited a difference in restriction sites between the vWF gene and the pseudogene and have designed allele-specific oligomer used with PCR to distinguish these two genes. Three candidate missense mutations; Ser743 (TCG) → Leu (TTG), Leu799 (CTG) → Pro (CCG), and Arg834 (CGG) → Trp (TGG) were identified in 4 out of 6 patients. The amino acid substitution at Arg834 has been reported previously, but the other substitutions at Ser743 and Leu799 are novel candidate mutations locating 99 and 43 amino acids to the N-terminal side of the cleavage site, respectively. Our results indicate that amino acid substitutions located relatively distant from the cleavage site may also be involved in type IIA vWD.

 

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