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Thromb Haemost 2000; 84(04): 536-540
DOI: 10.1055/s-0037-1614063
Review Article
Schattauer GmbH

Molecular Characterization of a Multiethnic Group of 21 Patients with Type 3 von Willebrand Disease

Luciano Baronciani
2   From the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, IRCCS Maggiore Hospital and University of Milan, Italy
,
Giovanna Cozzi
2   From the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, IRCCS Maggiore Hospital and University of Milan, Italy
,
Maria Teresa Canciani
2   From the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, IRCCS Maggiore Hospital and University of Milan, Italy
,
Flora Peyvandi
2   From the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, IRCCS Maggiore Hospital and University of Milan, Italy
,
Alok Srivastava
1   Department of Hematology, Christian Medical College Hospital, Vellore, India
,
Augusto Bramante Federici
2   From the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, IRCCS Maggiore Hospital and University of Milan, Italy
,
Pier Mannuccio Mannucci
2   From the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, IRCCS Maggiore Hospital and University of Milan, Italy
› Author AffiliationsWe would like to thank Dr. P. V. Jenkins (Royal Free Hospital, London, UK) for helpful criticism and advice. The financial support of the Foundation Angelo Bianchi Bonomi and Foundation Luigi Villa is gratefully acknowledged.
Further Information

Publication History

Received 12 April 2000

Accepted after revision 06 July 2000

Publication Date:
11 December 2017 (online)

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Summary

Type 3 von Willebrand disease is a rare autosomal disorder characterized by unmeasurable levels of von Willebrand factor and severe hemorrhagic symptoms. We studied a multiethnic group of 37 patients, from Italy (n = 14), Iran (n = 10) and India (n = 13) to identify the molecular defects and to evaluate genetic heterogeneity among these populations. Twenty-one patients (6 Italians, 9 Iranians and 6 Indians) were fully characterized at the molecular level. Twenty-four different gene alterations were identified, 20 of which have not been described previously. The majority of the mutations caused null alleles, 11 being nonsense mutations (Q218*, W222*, R365*, R373*, E644*, Q706*, S1338*, Q1346*, Y1542*, R1659*, E2129*), 4 small deletions (437delG, 2680delC, 6431delT, del 8491-8499), 3 possible splice site mutations [IVS9(-1)g→a, IVS29(+10)c→t, IVS40(-1)g → c], 3 candidate missense mutations (C275S, C2174G, C2804Y), 2 small insertions (7375insC, 7921insC) and 1 large gene deletion. The latter mutation was associated with the development of alloantibodies to VWF, but this complication was also found in a patient homozygous for a nonsense mutation (Q1346*). Due to the ethnic origin of the patients most of them were the offspring of consanguineous marriages and so were homozygous for the mutations found (18/21). Our results indicate that molecular defects responsible for type 3 VWD are scattered throughout the entire VWF gene (from exon 3 to 52), and that there is no prevalent and common gene defect in the three populations studied by us.

Keywords

von Willebrand factor - type 3 von Willebrand disease - gene analysis - mutation
 

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