Korean J Lab Med.  2007 Jun;27(3):169-176. 10.3343/kjlm.2007.27.3.169.

Investigation of von Willebrand Factor Gene Mutations in Korean von Willebrand Disease Patients

• Song J
• Choi JR
• Song KS

• KMID: 1781479
• DOI: http://doi.org/10.3343/kjlm.2007.27.3.169

Abstract

BACKGROUND: We intended to find the mutations of von Willebrand factor (VWF) gene as the most important contributing factor of von Willebrand disease (VWD) in Korean patients. METHODS: In 40 known vWD patients mutations of vWF gene were sought by direct sequencing of PCR products targeting exons 18, 19, 20, 26, 28 and 52 frequently implicated as the locations of mutation. For factors other than VWF gene contributing to VWD phenotype, we tested ABO blood group and measured ADAMTS13 activity in VWD patients. RESULTS: Twenty-seven cases (67.5%) were type 1 vWD, 3 cases (7.5%) type 3, and 5 cases (12.5%) type 2A. Three cases were type 2A or 2B (7.5%) and 2 cases were suspected to be type 2N (5.0%). Among them six candidate missense mutations were found: V1279I, R1306W, R1308C, and V1316M were previously reported in type 2B and type 1 vWD, and C858W and T1477I were novel findings. All patients were heterozygotes. Blood group O was overly represented in VWD patients, while ADAMTS13 activity of the patients was not significantly different from that of normal control. CONCLUSIONS: Mutation of VWF gene detected by genetic studies can significantly improve the diagnostic accuracy, especially in subtype assignment of VWD. Two novel mutations, C858W and T1477I associated with VWD were found and expected to contribute to the elucidation of its pathophysiology.

Keyword

von Willebrand disease; von Willebrand gene; ADAMTS13

MeSH Terms

ABO Blood-Group System
ADAM Proteins/analysis
Heterozygote
Humans
Korea
*Mutation, Missense
Polymerase Chain Reaction
Polymorphism, Genetic
Sequence Analysis, DNA
von Willebrand Disease/classification/diagnosis/*genetics
von Willebrand Factor/analysis/*genetics

Figure

• 

  Fig. 1. The probable role of the novel findings C858W and T1477I in causing VWD. The C858W segregated with decreased VWF activity within the family of the patient 37, while mildly decreased VWF: Ag was observed in all members of the family (A). The residues 858C and 1477T (indicated by asterisk) within VWF are more strictly preserved throughout several different mammalian species than other immediate neighboring residues, implying its essentiality for wholeness of VWF in regard to its synthesis, stability or function (B, C).

• 

  Fig. 2. ADAMTS13 activity in VWD patients compared with normal controls. There was no significant difference between ADAMTS13 activity between VWD patients (n=38) and normal healthy control (n=38).

Reference

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