title: Genetic defects leading to hereditary thrombotic thrombocytopenic purpura.
abstract: In patients with thrombotic thrombocytopenic purpura (TTP), unusually large multimers of von Willebrand factor (VWF) circulate in the plasma. This is caused by a functional deficiency of VWF-cleaving protease, ADAMTS-13. Although TTP usually occurs as an acquired form due to autoantibodies against ADAMTS-13, the condition may be inherited in an autosomal recessive fashion. Thus far, genomic DNA from 23 patients with hereditary TTP and their families has been analyzed and 33 causative mutations identified in the ADAMTS13 gene: 19 missense, five nonsense, five frameshift, and four splice mutations. Common missense polymorphisms have been also found, one of which significantly reduces ADAMTS-13 activity. No cases have been found without mutations in the ADAMTS13 gene, suggesting that genetic defects in ADAMTS13 are the dominant cause of hereditary TTP. Further analysis may reveal the genetic background associated with acquired TTP and other thrombotic diseases.
authors.affiliation: National Cardiovascular Center Research Institute, Suita, Osaka, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kokame
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miyata
mesh_terms: D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; D006801:Humans; D008666:Metalloendopeptidases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011697:Purpura, Thrombotic Thrombocytopenic / Q000235:genetics* / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D014841:von Willebrand Factor; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human