title: [Hereditary form of thrombotic thrombocytopenic purpura].
abstract: BACKGROUND
  Thrombotic thrombocytopenic purpura is characterized by microvascular platelet clumping resulting in thrombocytopenia, microangiopathic hemolysis, neurological abnormality, and renal dysfunction. Similar manifestations also occur in patients with the hemolytic uremic syndrome or other types of disorders. Recent studies demonstrate that severe deficiency of the von Willebrand factor cleaving metalloprotease, ADAMTS 13, causes thrombotic thrombocytopenic purpura. Aim of our study was to characterize gene defects causing inherited type of disease.
  
  
  RESULTS
  We investigated nine patients with recurrent type of disease with familiar origin and twelve relatives. Samples were taken in a remission of disease. We measured activity of ADAMTS13 (vWF-CP) with modified method of the quantitative immunoblotting of degraded vWF multimers. Mutation screening was carried out by sequencing all 29 exons and flanking intron regions of the ADAMTS13 gene. Five distinct mutations were found. Three of them are novel.
  
  
  CONCLUSIONS
  Mutation analysis of the ADAMTS 13 gene brought interesting results in eight patients. We found a one single base frameshift insertion, 4143insA in 8 of 9 unrelated individuals. This investigation represents an advantage in the differential diagnosis of disease since the thrombotic thrombocytopenic purpura phenotype in childhood can be variable and rapid detection of mutation is helpful for the recurrence prevention.
authors.affiliation: Ustav hematologie a krevní transfuze, Praha. ingrid.hrachovinova@uhkt.cz
authors.forename: I
authors.initials: I
authors.lastname: Hrachovinová
authors.forename: S
authors.initials: S
authors.lastname: Rittich
authors.forename: P
authors.initials: P
authors.lastname: Salaj
authors.forename: J
authors.initials: J
authors.lastname: Suttnar
authors.forename: J E
authors.initials: JE
authors.lastname: Dyr
authors.forename: T
authors.initials: T
authors.lastname: Suláková
authors.forename: J
authors.initials: J
authors.lastname: Pták
authors.forename: P
authors.initials: P
authors.lastname: Dulícek
authors.forename: T
authors.initials: T
authors.lastname: Seeman
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D000071120:ADAMTS13 Protein; D002648:Child; D016368:Frameshift Mutation; D006801:Humans; D009154:Mutation; D011697:Purpura, Thrombotic Thrombocytopenic / Q000235:genetics*; D014841:von Willebrand Factor / Q000235:genetics
chemical_list: D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human