Subscribe to RSS
DOI: 10.1160/TH05-12-0817
A common origin of the 4143insA ADAMTS13 mutation
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.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.
-
References
- 1 Gerritsen HE, Robles R, Lämmle B. et al. Partial amino acid sequence of purified von Willebrand factorcleaving protease. Blood 2001; 98: 1654-61.
- 2 Fujikawa K, Suzuki H, McMullen B. et al. Purification of human von Willebrand factor-cleaving protease and its identification as a new member of the metalloproteinase family. Blood 2001; 98: 1662-6.
- 3 Levy GG, Nichols WC, Lian EC. et al. Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature 2001; 413: 488-94.
- 4 Soejima K, Mimura N, Hirashima M. et al. A novel human metalloprotease synthesized in the liver and secreted into the blood: possibly, the von Willebrand factor-cleaving protease?. J Biochem 2001; 130: 475-80.
- 5 Moschcowitz E. Hyaline thrombosis of the terminal arterioles and capillaries: a hitherto undescribed disease. Proc NY Pathol Soc 1924; 24: 21-4.
- 6 Schneppenheim R, Budde U, Oyen F. et al. Von Willebrand factor cleaving protease and ADAMTS13 mutations in childhood TTP. Blood 2003; 101: 1845-50.
- 7 Kokame K, Matsumoto M, Soejima K. et al. Mutations and common polymorphisms in ADAMTS13 gene responsible for von Willebrand factor-cleaving protease activity. Proc Natl Acad Sci USA 2002; 99: 11902-7.
- 8 Antoine G, Zimmermann K, Plaimauer B. et al. ADAMTS13 gene defects in two brothers with constitutional thrombotic thrombocytopenic purpura and normalization of von Willebrand factor-cleaving protease activity by recombinant human ADAMTS13. Br J Haematol 2003; 120: 821-4.
- 9 Assink K, Schiphorst R, Allford S. et al. Mutation analysis and clinical implications of von Willebrand factor-cleaving protease deficiency. Kidney International 2003; 63: 1995-9.
- 10 Savasan S, Lee SK, Ginsburg D. et al. ADAMTS13 gene mutation in congenital thrombotic thrombocytopenic purpura with previously reported normal VWF cleaving protease activity. Blood 2003; 101: 4449-51.
- 11 Pimanda JE, Maekawa A, Wind T. et al. Congenital thrombotic thrombocytopenic purpura in association with a mutation in the second CUB domain of ADAMTS13. Blood 2004; 103: 627-9.
- 12 Matsumoto M, Kokame K, Soejima K. et al. Molecular characterization of ADAMTS13 gene mutations in Japanese patients with Upshaw-Schulman syndrome. Blood 2004; 103: 1305-10.
- 13 Veyradier A, Lavergne J-M, Ribba A-S. et al. Ten candidate ADAMTS13 mutations in six French families with congenital thrombotic thrombocytopenic purpura (Upshaw-Schulman syndrome). J Thromb Haemost 2004; 02: 424-9.
- 14 Uchida T, Wada H, Mizutani M. et al. Identification of novel mutations in ADAMTS13 in an adult patient with congenital thrombotic thrombocytopenic purpura. Blood 2004; 104: 2081-3.
- 15 Peyvandi F, Ferrari S, Lavoretano S. et al. Von Willebrand factor cleaving protease (ADAMTS-13) and ADAMTS-13 neutralizing autoantibodies in 100 patients with thrombotic thrombocytopenic purpura. Br J Haematol 2004; 127: 433-9.
- 16 Häberle J, Kehrel B, Ritter J. et al. New strategies in diagnosis and treatment of thrombotic thrombocytopenic purpura: case report and review. Eur J Pediatr 1999; 158: 883-7.
- 17 Becker T, Knapp M. Maximum-likelihood estimation of haplotype frequencies in nuclear families. Genet Epidemiol 2004; 27: 21-32.
- 18 Zhang ZP, Falk G, Blomback M. et al. A single cytosine deletion in exon 18 of the von Willebrand factor gene is the most common mutation in Swedish vWD type III patients. Hum Mol Genet 1992; 01: 767-8.
- 19 Gazda H, Budde U, Krey S. et al. Delta C in exon 18 of the von Willebrand factor gene is the most common mutation in patients with severe von Willebrand disease type3 in Poland. Blood 1997; (90) (Suppl) 3132.
- 20 Schneppenheim R, Krey S, Bergmann F. et al. Genetic heterogeneity of severe von Willebrand disease type III in the German population. Hum Genet 1994; 94: 640-52.