title: ADAMTS13 gene mutation in congenital thrombotic thrombocytopenic purpura with previously reported normal VWF cleaving protease activity.
abstract: Deficiency of von Willebrand factor (VWF) cleaving protease ADAMTS13 is associated with the development of thrombotic thrombocytopenic purpura (TTP). A case of congenital TTP that was previously reported to have normal ADAMTS13 activity was analyzed at the molecular level. Reanalysis of plasma VWF cleaving protease activity using a different assay revealed that the patient had less than 0.1 U/L ADAMTS13 protease activity, while the parents were both partially deficient. Sequence analysis of DNA amplified by polymerase chain reaction showed that the patient was homozygous for a novel TT deletion in exon 15 of the ADAMTS13 gene resulting in a frameshift, while both parents were heterozygous for the same mutation. Taken together with other recent reports, all the cases of hereditary TTP studied by DNA sequence analysis to date appear to be due to mutations within the ADAMTS13 gene.
authors.affiliation: Children's Hospital of Michigan, Division of Hematology/Oncology, Wayne State University, Detroit, MI, USA.
authors.forename: Sureyya
authors.initials: S
authors.lastname: Savasan
authors.forename: Soon-Ki
authors.initials: SK
authors.lastname: Lee
authors.forename: David
authors.initials: D
authors.lastname: Ginsburg
authors.forename: Han-Mou
authors.initials: HM
authors.lastname: Tsai
mesh_terms: D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; D004252:DNA Mutational Analysis; D005091:Exons; D005192:Family Health; D005260:Female; D016368:Frameshift Mutation; D006720:Homozygote; D006801:Humans; D015151:Immunoblotting; D008666:Metalloendopeptidases / Q000235:genetics* / Q000378:metabolism; D011697:Purpura, Thrombotic Thrombocytopenic / Q000151:congenital / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human