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Blood, 15 February 2004, Vol. 103, No. 4, pp. 1305-1310. Prepublished online as a Blood First Edition Paper on October 16, 2003; DOI 10.1182/blood-2003-06-1796. This Article Full Text (PDF) All Versions of this Article: 2003-06-1796v1 103/4/1305    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Matsumoto, M. Articles by Fujimura, Y. Search for Related Content PubMed PubMed Citation Articles by Matsumoto, M. Articles by Fujimura, Y. Social Bookmarking                   What's this? Submitted June 12, 2003 Accepted September 29, 2003 Molecular characterization of ADAMTS13 gene mutations in Japanese patients with Upshaw-Schulman syndrome Masanori Matsumoto, Koichi Kokame, Kenji Soejima, Masayoshi Miura, Syuhei Hayashi, Yasuhiko Fujii, Asayuki Iwai, Etsuro Ito, Yoichiro Tsuji, Mayuko Takeda-Shitaka, Mitsuo Iwadate, Hideaki Umeyama, Hideo Yagi, Hiromichi Ishizashi, Fumiaki Banno, Tomohiro Nakagaki, Toshiyuki Miyata, and Yoshihiro Fujimura* Departments of Blood Transfusion Medicine and Health Science, Nara Medical University, Kashihara, Nara, Japan National Cardiovascular Center Research Institute, Osaka, Japan First Research Department, The Chemo-Sero-Therapeutic Reseach Institute, Kikuchi, Kumamoto, Japan Department of Pediatrics, Toyama City Hosipital, Toyama, Japan Department of Pediatrics, Fukui Red Cross Hospital, Fukui, Japan Department of Blood Transfusion Medicine, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan Department of Pediatrics, Kagawa Children's Hospital, Zentsuji, Kagawa, Japan Department of Pediatrics, Hirosaki University School of Medicine, Hirosaki, Aomori, Japan Department of Pediatrics, Tokyo Medical and Dental University, Tokyo, Japan School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan * Corresponding author; email: yfujimur{at}naramed-u.ac.jp. We report here seven new mutations in the ADAMTS13 gene responsible for Upshaw-Schulman syndrome (USS), a catastrophic phenotype of congenital thrombotic thrombocytopenic purpura, by analyzing five Japanese families. Three mutations occurred at exon-intron boundaries: 414+1G>A at intron 4, 686+1G>A at intron 6, and 1244+2T>G at intron 10 (numbered from the A of the initiation Met codon), and we confirmed that two of these mutations produced aberrantly spliced mRNAs. The remaining four mutations were missense mutations: R193W, I673F, C908Y, and R1123C. In expression experiments using HeLa cells, all mutants showed no or a marginal secretion of ADAMTS-13. Taken together with the findings in our recent report (Kokame et al Proc Natl Acad Sci USA.2002;99:11902-11907), we determined the responsible mutations in a total of seven Japanese patients with USS with a uniform clinical picture of severe neonatal hyperbilirubinemia, and in their family members, based on ADAMTS13 gene analysis. Of these patients, two were homozygotes and five were compound heterozygotes. The parents of one homozygote were related (cousins), while those of the other were not. Molecular models of the metalloprotease, Tsp1-5 and Tsp1-8 domains of ADAMTS-13 suggest that the missense mutations could cause structural defects in the mutants. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Galbusera, M. Noris, and G. Remuzzi Inherited thrombotic thrombocytopenic purpura Haematologica, February 1, 2009; 94(2): 166 - 170. [Full Text] [PDF] B. Lammle, J. A. Kremer Hovinga, and J. N. George Acquired thrombotic thrombocytopenic purpura: ADAMTS13 activity, anti-ADAMTS13 autoantibodies and risk of recurrent disease Haematologica, February 1, 2008; 93(2): 172 - 177. [Full Text] [PDF] J. Song, K. A Lee, T. S. Park, R. Park, and J. R. 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