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

Reinhard Schneppenheim
1  University Medical Center Hamburg-Eppendorf, Department of Pediatric Hematology and Oncology, Hamburg, Germany
,
Johanna A. Kremer Hovinga
2  Department of Hematology and Central Hematology Laboratory, University Hospital, Inselspital, Bern, Switzerland
,
Tim Becker
3  University Bonn, Institute for Medical Biometrics, Informatics and Epidemiology, Bonn, Germany
,
Ulrich Budde
4  Laboratory Association Prof. Arndt and Partners, Coagulation Lab, Hamburg, Germany
,
Diana Karpman
5  Department of Pediatrics, Lund University, Lund, Sweden
,
Wolfgang Brockhaus
6  Klinikum Nürnberg, Department of Angiology and Coagulation Disorders, Nürnberg, Germany
,
Ingrid Hrachovinová
7  Institute of Hematology and Blood Transfusion, Coagulation Lab, Praha, Czech Republic
,
Bartosz Korczowski
8  Department of Pediatrics, Regional Hospital, University of Rzeszów, Rzeszów, Poland
,
Florian Oyen
1  University Medical Center Hamburg-Eppendorf, Department of Pediatric Hematology and Oncology, Hamburg, Germany
,
Šimon Rittich
7  Institute of Hematology and Blood Transfusion, Coagulation Lab, Praha, Czech Republic
,
Johannes von Rosen
9  Department of Pediatrics Länssjukhuset Ryhov, Jönköping, Sweden
,
Geir E. Tjønnfjord
10  Rikshospitalet, University Hospital, Medical Department, Oslo, Norway
,
John E. Pimanda
11  Cambridge Institute for Medical Research, University of Cambridge, UK
,
Thomas F. Wienker
3  University Bonn, Institute for Medical Biometrics, Informatics and Epidemiology, Bonn, Germany
,
Bernhard Lämmle
2  Department of Hematology and Central Hematology Laboratory, University Hospital, Inselspital, Bern, Switzerland
› Author Affiliations
Financial support: This work was supported by grants from the German Society on Thrombosis and Hemostasis (GTH) and the National Genome Research Network (NGFN2): Cardiovascular diseases provided by the German Federal Ministry of Education and Research (project no. NHK-S17T22) both to RS, the Mach-Gaensslen Foundation Switzerland(to JAKH), the Swiss National Foundation for Scientific Research (Grant no. 3200B0–108261) to JAKH and BL, the Swedish Research Council (06X-14008) and the Crafoord Foundation both to DK, the National Health and Medical Research Council of Australia to JEP, and by a grant from the Czech Ministry of Health (IGA N M/7719–3) to IH and SR.
Further Information

Publication History

Received 22 December 2005

Accepted after resubmission 26 May 2006

Publication Date:
29 November 2017 (online)

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.