title: Novel ADAMTS-13 mutations in an adult with delayed onset thrombotic thrombocytopenic purpura.
abstract: BACKGROUND
  Thrombotic thrombocytopenic purpura (TTP) is associated with congenital and acquired deficiency of ADAMTS-13, a metalloprotease that cleaves von Willebrand factor (VWF) and reduces its adhesive activity. Mutations throughout the ADAMTS13 gene have been identified in congenital TTP patients, most of whom have initial episodes during infancy or in early childhood.
  
  
  METHODS
  We report the case of an adult male who was diagnosed with idiopathic thrombocytopenic purpura at age 34, and with TTP 14 years later. The patient was compound heterozygous for an 18 bp in-frame deletion (C365del) in the disintegrin domain and a point mutation of R1060W in the seventh thrombospondin domain of the ADAMTS-13 gene.
  
  
  CONCLUSIONS
  In vitro studies found that C365del and R1060W severely impair ADAMTS-13 synthesis in transfected Hela cells, whereas the deletion mutant also failed to cleave VWF under static and flow conditions.
authors.affiliation: Section of Thrombosis Research, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Tao
authors.forename: K
authors.initials: K
authors.lastname: Anthony
authors.forename: Y
authors.initials: Y
authors.lastname: Peng
authors.forename: H
authors.initials: H
authors.lastname: Choi
authors.forename: L
authors.initials: L
authors.lastname: Nolasco
authors.forename: L
authors.initials: L
authors.lastname: Rice
authors.forename: J L
authors.initials: JL
authors.lastname: Moake
authors.forename: J-F
authors.initials: JF
authors.lastname: Dong
mesh_terms: D051722:ADAM Proteins / Q000096:biosynthesis / Q000235:genetics*; D000071120:ADAMTS13 Protein; D000328:Adult; D017668:Age of Onset; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D017354:Point Mutation; D011696:Purpura, Thrombocytopenic / Q000473:pathology; D011697:Purpura, Thrombotic Thrombocytopenic; D017384:Sequence Deletion
chemical_list: D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human