Congenital thrombotic thrombocytopenic purpura in association with a mutation in the second CUB domain of ADAMTS13.
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Pimanda JE, Maekawa A, Wind T, Paxton J, Chesterman CN, Hogg PJ
Congenital thrombotic thrombocytopenic purpura in association with a mutation in the second CUB domain of ADAMTS13.
Blood. 2004 Jan 15;103(2):627-9. doi: 10.1182/blood-2003-04-1346. Epub 2003 Sep 25.
- PubMed ID
- 14512317 [ View in PubMed]
- Abstract
Severe deficiency of the von Willebrand Factor (VWF)-cleaving proteinase, ADAMTS13, is associated with the development of thrombotic thrombocytopenic purpura (TTP). Several mutations spread across the ADAMTS13 gene have been identified in association with a deficiency of VWF-cleaving proteinase activity in patients with congenital TTP. The spread of these dysfunctional mutations and the domain structure of ADAMTS13 are suggestive of a complex interaction between the enzyme and its substrate. We have studied a patient with congenital TTP who is a compound heterozygote for the Thr196Ile mutation in the metalloproteinase domain and a frameshift mutation (4143-4144insA) in the second CUB domain that results in loss of the last 49 amino acids of the protein. The VWF-cleaving proteinase activity of the truncated enzyme was comparable to that of the wild-type enzyme but its secretion from transfected COS-7 cells was about 14% of the wild type.