title: Congenital thrombotic thrombocytopenic purpura in association with a mutation in the second CUB domain of ADAMTS13.
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.
mesh_terms: D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D019556:COS Cells; D002522:Chlorocebus aethiops; D016368:Frameshift Mutation; D006801:Humans; D008666:Metalloendopeptidases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008958:Models, Molecular; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011487:Protein Conformation; D011697:Purpura, Thrombotic Thrombocytopenic / Q000151:congenital* / Q000235:genetics*; D014162:Transfection; D014841:von Willebrand Factor / Q000235:genetics
chemical_list: D014841:von Willebrand Factor; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human