A common origin of the 4143insA ADAMTS13 mutation

Reinhard Schneppenheim; Johanna A. Kremer Hovinga; Tim Becker; Ulrich Budde; Diana Karpman; Wolfgang Brockhaus; Ingrid Hrachovinová; Bartosz Korczowski; Florian Oyen; Šimon Rittich; Johannes von Rosen; Geir E. Tjønnfjord; John E. Pimanda; Thomas F. Wienker; Bernhard Lämmle

doi:10.1160/TH05-12-0817

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2006; 96(01): 3-6
DOI: 10.1160/TH05-12-0817

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

A common origin of the 4143insA ADAMTS13 mutation

Authors

Reinhard Schneppenheim

¹University Medical Center Hamburg-Eppendorf, Department of Pediatric Hematology and Oncology, Hamburg, Germany
Johanna A. Kremer Hovinga

²Department of Hematology and Central Hematology Laboratory, University Hospital, Inselspital, Bern, Switzerland
Tim Becker

³University Bonn, Institute for Medical Biometrics, Informatics and Epidemiology, Bonn, Germany
Ulrich Budde

⁴Laboratory Association Prof. Arndt and Partners, Coagulation Lab, Hamburg, Germany
Diana Karpman

⁵Department of Pediatrics, Lund University, Lund, Sweden
Wolfgang Brockhaus

⁶Klinikum Nürnberg, Department of Angiology and Coagulation Disorders, Nürnberg, Germany
Ingrid Hrachovinová

⁷Institute of Hematology and Blood Transfusion, Coagulation Lab, Praha, Czech Republic
Bartosz Korczowski

⁸Department of Pediatrics, Regional Hospital, University of Rzeszów, Rzeszów, Poland
Florian Oyen

¹University Medical Center Hamburg-Eppendorf, Department of Pediatric Hematology and Oncology, Hamburg, Germany
Šimon Rittich

⁷Institute of Hematology and Blood Transfusion, Coagulation Lab, Praha, Czech Republic
Johannes von Rosen

⁹Department of Pediatrics Länssjukhuset Ryhov, Jönköping, Sweden
Geir E. Tjønnfjord

¹⁰Rikshospitalet, University Hospital, Medical Department, Oslo, Norway
John E. Pimanda

¹¹Cambridge Institute for Medical Research, University of Cambridge, UK
Thomas F. Wienker

³University Bonn, Institute for Medical Biometrics, Informatics and Epidemiology, Bonn, Germany
Bernhard Lämmle

²Department of Hematology and Central Hematology Laboratory, University Hospital, Inselspital, Bern, Switzerland

Abstract

Summary

Severely deficient activity of the von Willebrand Factor (VWF) cleaving metalloprotease,ADAMTS13, is associated with thrombotic thrombocytopenic purpura (TTP).The mutation spectrum of ADAMTS13 is rather heterogeneous,and numerous mutations spread across the gene have been described in association with congenital TTP. The 4143insA mutation is unusual with respect to its geographic concentration. Following the initial report from Germany in which the 4143insA mutation was detected in four apparently unrelated families, we have now identified this mutation in a further eleven patients from Norway, Sweden, Poland, Germany, the Czech Republic and Australia. Confirmation that the Australian patient is of German ancestry, together with the Northern and Central European origin of most of the other patients, suggests that the 4143insA mutation has a common genetic background. We established ADAMTS13 haplotypes by analyzing 17 polymorphic intragenic markers. The haplotypes linked to 4143insA were identical in all informative families. Three novel candidate mutations, C347S, P671L and R1060W, as well as the known mutation R507Q, were also identified during the course of the study. We conclude that 4143insA has a common genetic background and is frequent among patients with hereditary ADAMTS13 deficiency in Northern and Central European countries.

Keywords

ADAMTS13 - TTP - VWF - mutation

Full Text

References

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