VWF-cleaving proteinase activity and ADAMTS13 mutations in a patient with congenital TTP. (A) The pedigree with the ADAMTS13 activity levels of the father (I-1), the mother (I-2), the patient (II-1), and the patient's brother (II-2). The values are expressed as a percentage of VWF-cleaving proteinase activity in normal pooled human plasma. (B) The 1427–amino acid precursor protein of ADAMTS13 contains a signal peptide (SP), a propeptide (Pro), a metalloprotease domain (MP), a disintegrin-like domain (Dis), a type-1 TSP module (T), a cysteine-rich (Cys) and spacer domain, 7 additional type-1 TSP modules, and 2 CUB (complement components C1r/C1s, sea urchin epidermal growth factor, and bone morphogenetic protein) domains. The mutation at Thr196Ile on exon 6 is positioned within the metalloprotease domain and the mutation after Ser1381 truncates the second CUB domain of the protein.