Three distinct candidate point mutations of the von Willebrand factor gene in four patients with type IIA von Willebrand disease

I. Sugiura, T. Matsushita, M. Tanimoto, I. Takahashi, T. Yamazaki, K. Yamamoto, J. Takamatsu, T. Kamiya, H. Saito

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)612-617
Number of pages6
JournalThrombosis and Haemostasis
Volume67
Issue number6
Publication statusPublished - 1992
Externally publishedYes

Fingerprint

Type 2 von Willebrand Disease
von Willebrand Factor
Point Mutation
Genes
Missense Mutation
Amino Acid Substitution
Polymerase Chain Reaction
Pseudogenes
Proteolysis
Alleles
Amino Acids
Mutation

ASJC Scopus subject areas

  • Hematology

Cite this

Sugiura, I., Matsushita, T., Tanimoto, M., Takahashi, I., Yamazaki, T., Yamamoto, K., ... Saito, H. (1992). Three distinct candidate point mutations of the von Willebrand factor gene in four patients with type IIA von Willebrand disease. Thrombosis and Haemostasis, 67(6), 612-617.

Three distinct candidate point mutations of the von Willebrand factor gene in four patients with type IIA von Willebrand disease. / Sugiura, I.; Matsushita, T.; Tanimoto, M.; Takahashi, I.; Yamazaki, T.; Yamamoto, K.; Takamatsu, J.; Kamiya, T.; Saito, H.

In: Thrombosis and Haemostasis, Vol. 67, No. 6, 1992, p. 612-617.

Research output: Contribution to journalArticle

Sugiura, I, Matsushita, T, Tanimoto, M, Takahashi, I, Yamazaki, T, Yamamoto, K, Takamatsu, J, Kamiya, T & Saito, H 1992, 'Three distinct candidate point mutations of the von Willebrand factor gene in four patients with type IIA von Willebrand disease', Thrombosis and Haemostasis, vol. 67, no. 6, pp. 612-617.
Sugiura I, Matsushita T, Tanimoto M, Takahashi I, Yamazaki T, Yamamoto K et al. Three distinct candidate point mutations of the von Willebrand factor gene in four patients with type IIA von Willebrand disease. Thrombosis and Haemostasis. 1992;67(6):612-617.
Sugiura, I. ; Matsushita, T. ; Tanimoto, M. ; Takahashi, I. ; Yamazaki, T. ; Yamamoto, K. ; Takamatsu, J. ; Kamiya, T. ; Saito, H. / Three distinct candidate point mutations of the von Willebrand factor gene in four patients with type IIA von Willebrand disease. In: Thrombosis and Haemostasis. 1992 ; Vol. 67, No. 6. pp. 612-617.
@article{cf48f31f02494b43bbcf144ec1a09af8,
title = "Three distinct candidate point mutations of the von Willebrand factor gene in four patients with type IIA von Willebrand disease",
abstract = "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.",
author = "I. Sugiura and T. Matsushita and M. Tanimoto and I. Takahashi and T. Yamazaki and K. Yamamoto and J. Takamatsu and T. Kamiya and H. Saito",
year = "1992",
language = "English",
volume = "67",
pages = "612--617",
journal = "Thrombosis and Haemostasis",
issn = "0340-6245",
publisher = "Schattauer GmbH",
number = "6",

}

TY - JOUR

T1 - Three distinct candidate point mutations of the von Willebrand factor gene in four patients with type IIA von Willebrand disease

AU - Sugiura, I.

AU - Matsushita, T.

AU - Tanimoto, M.

AU - Takahashi, I.

AU - Yamazaki, T.

AU - Yamamoto, K.

AU - Takamatsu, J.

AU - Kamiya, T.

AU - Saito, H.

PY - 1992

Y1 - 1992

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0026748293&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026748293&partnerID=8YFLogxK

M3 - Article

C2 - 1380739

AN - SCOPUS:0026748293

VL - 67

SP - 612

EP - 617

JO - Thrombosis and Haemostasis

JF - Thrombosis and Haemostasis

SN - 0340-6245

IS - 6

ER -