Von Willebrand disease type 2M 'Vicenza' in Italian and German patients: Identification of the first candidate mutation (G3864A; R1205H) in 8 families

Reinhard Schneppenheim, Augusto B. Federici, Ulrich Budde, Giancarlo Castaman, Elke Drewke, Sonja Krey, Pier M. Mannucci, Gabi Riesen, Francesco Rodeghiero, Barbara Zieger, Rainer Zimmermann

Research output: Contribution to journalArticle

Abstract

Von Willebrand disease type 2M 'Vicenza' (VWD 2M V) is characterised by autosomal dominant inheritance, low von Willebrand factor (VWF) and the presence of 'supranormal' multimers in plasma. This specific phenotype has been described in Italian and recently also in German patients. The molecular defect is linked to the VWF gene. However, no specific mutations have been identified until now. We analysed the complete coding region and adjacent intron sequences of the VWF gene in Italian families in comparison to German families with VWD 2M V by a PCR-based mutation screening, combined with SSC- and heteroduplex-analysis of exons 2 through 52, followed by direct sequencing. We identified the first heterozygous candidate mutation (G3864A: R1205H) in all affected members of the 7 Italian families and in 1 German patient but not in the unaffected family members nor on 100 chromosomes of normal subjects, suggesting a causal relationship between the mutation and the phenotype. Haplotype identity, with minor deviations in one Italian family, suggests a common but not very recent genetic origin of R1205H.

Original languageEnglish
Pages (from-to)136-140
Number of pages5
JournalThrombosis and Haemostasis
Volume83
Issue number1
Publication statusPublished - 2000

Keywords

  • Von Willebrand disease type 2M Vicenza
  • Von Willebrand factor genetics

ASJC Scopus subject areas

  • Hematology

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    Schneppenheim, R., Federici, A. B., Budde, U., Castaman, G., Drewke, E., Krey, S., Mannucci, P. M., Riesen, G., Rodeghiero, F., Zieger, B., & Zimmermann, R. (2000). Von Willebrand disease type 2M 'Vicenza' in Italian and German patients: Identification of the first candidate mutation (G3864A; R1205H) in 8 families. Thrombosis and Haemostasis, 83(1), 136-140.