title: Identification of novel mutations in ADAMTS13 in an adult patient with congenital thrombotic thrombocytopenic purpura.
abstract: Congenital thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) is associated with an inherited von Willebrand factor-cleaving protease (ADAMTS13 [a disintegrin and metalloprotease with thrombospondin type I domains 13]) deficiency. In this study, we identified novel mutations in the ADAMTS13 gene in a patient with TTP. The patient was a 51-year-old Japanese male who exhibited TTP symptoms at frequent intervals. The ADAMTS13 activity during acute episodes was less than 3% that of normal. The enzyme activities of the patient's father and mother were both 46%, and both parents were asymptomatic. Genetic analysis revealed that the patient was a compound heterozygote for 2 mutations. One mutation was a missense mutation in the metalloprotease domain (A250V, exon 7), and the other was a guanine to adenine substitution at the 5' end of intron 3 (intron 3 G-->A). In vitro expression studies revealed that the A250V mutation markedly reduced ADAMTS13 activity and the intron 3 G-->A mutation caused abnormal mRNA synthesis.
authors.affiliation: New Product Laboratories II, Daiichi Pharmaceutical, Tokyo, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Uchida
authors.forename: Hideo
authors.initials: H
authors.lastname: Wada
authors.forename: Minoru
authors.initials: M
authors.lastname: Mizutani
authors.forename: Miho
authors.initials: M
authors.lastname: Iwashita
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ishihara
authors.forename: Toshiro
authors.initials: T
authors.lastname: Shibano
authors.forename: Misako
authors.initials: M
authors.lastname: Suzuki
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Matsubara
authors.forename: Kenji
authors.initials: K
authors.lastname: Soejima
authors.forename: Masanori
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fujimura
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Murata
mesh_terms: D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; D000225:Adenine / Q000737:chemistry; D005091:Exons; D006147:Guanine / Q000737:chemistry; D006579:Heterozygote; D006801:Humans; D007438:Introns; D008297:Male; D008666:Metalloendopeptidases / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D010641:Phenotype; D017434:Protein Structure, Tertiary; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood / Q000235:genetics*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry
chemical_list: D012333:RNA, Messenger; D011994:Recombinant Proteins; D006147:Guanine; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human; D000225:Adenine