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

doi:10.1055/s-0037-1613769

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2000; 83(01): 136-140
DOI: 10.1055/s-0037-1613769

Commentary

Schattauer GmbH

Von Willebrand Disease Type 2M “Vicenza” in Italian and German Patients: Identification of the First Candidate Mutation (G3864A; R1205H) in 8 Families

Reinhard Schneppenheim

¹From the University Children’s Hospital Hamburg, Division of Paediatric Haematology and Oncology, Hamburg, Germany

,

Augusto B. Federici

²Angelo Bianchi Bonomi Haemophilia Thrombosis Centre, Department of Internal Medicine, IRCCS Maggiore Hospital and University of Milan, Italy

,

Ulrich Budde

³Lab Association Keeser, Arndt and Partners, Coagulation Laboratory, Hamburg, Germany

,

Giancarlo Castaman

⁴Haemophilia and Thrombosis Centre and Department of Haematology, San Bortolo Hospital, Vicenza, Italy

,

Elke Drewke

³Lab Association Keeser, Arndt and Partners, Coagulation Laboratory, Hamburg, Germany

,

Sonja Krey

⁵University Children’s Hospital Kiel

,

Pier M. Mannucci

²Angelo Bianchi Bonomi Haemophilia Thrombosis Centre, Department of Internal Medicine, IRCCS Maggiore Hospital and University of Milan, Italy

,

Gabi Riesen

⁵University Children’s Hospital Kiel

,

Francesco Rodeghiero

⁴Haemophilia and Thrombosis Centre and Department of Haematology, San Bortolo Hospital, Vicenza, Italy

,

Barbara Zieger

⁶University Children’s Hospital Freiburg

,

Rainer Zimmermann

⁷Rehabilitation Hospital, Heidelberg, Germany

› Author Affiliations

Abstract

Summary

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.

Keywords

Von Willebrand Disease Type 2M Vicenza - von Willebrand Factor Genetics

Full Text

References

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