Thromb Haemost 1994; 72(02): 180-185
DOI: 10.1055/s-0038-1648835
Original Article
Schattauer GmbH Stuttgart

Characterization of Partial Gene Deletions in Type III von Willebrand Disease with Alloantibody Inhibitors[*]

David J Mancuso
1  The Howard Hughes Medical Institute, The Jewish Hospital of St. Louis, Division of Hematology-Oncology, Departments of Medicine and Biochemistry & Molecular Biophysics, Washington University School of Medicine, St. Louis, USA
,
Elodee A Tuley
1  The Howard Hughes Medical Institute, The Jewish Hospital of St. Louis, Division of Hematology-Oncology, Departments of Medicine and Biochemistry & Molecular Biophysics, Washington University School of Medicine, St. Louis, USA
,
Ricardo Castillo
2  The Servicio de Hemoterapie y Hemostasia, Hospital Clínico y Provincial, Facultad de Medicina, Barcelona, Spain
,
Norma de Bosch
3  The Departamento de Investigaciones, Banco Municipal de Sangre, del Distrito Federal, Caracas, Venezuela
,
Pler M Mannucci
4  The Bianchi Bonomi Hemophilia and Thrombosis Center, Institute of Internal Medicine, University of Milano, Milano, Italy
,
J Evan Sadler
1  The Howard Hughes Medical Institute, The Jewish Hospital of St. Louis, Division of Hematology-Oncology, Departments of Medicine and Biochemistry & Molecular Biophysics, Washington University School of Medicine, St. Louis, USA
› Author Affiliations
Further Information

Publication History

Received 25 August 1993

Accepted after resubmission 21 April 1994

Publication Date:
24 July 2018 (online)

Summary

von Willebrand factor gene deletions were characterized in four patients with severe type III von Willebrand disease and alloantibodies to von Willebrand factor. A PCR-based strategy was used to characterize the boundaries of the deletions. Identical 30 kb von Willebrand factor gene deletions which include exons 33 through 38 were identified in two siblings of one family by this method. A small 5 base pair insertion (CCTGG) was sequenced at the deletion breakpoint. PCR analysis was used to detect the deletion in three generations of the family, including two family members who are heterozygous for the deletion. In a second family, two type III vWD patients, who are distant cousins, share an -56 kb deletion of exons 22 through 43. The identification and characterization of large vWF gene deletions in these type III vWD patients provides further support for the association between large deletions in both von Willebrand factor alleles and the development of inhibitory alloantibodies.

* Nucleotide sequences reported in this paper have been submitted to the GenBank/EMBL Data Bank under the accession number LI5333.