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Prepublished online as a Blood First Edition Paper on February 6, 2003; DOI 10.1182/blood-2002-11-3329. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-11-3329v1 101/11/4430    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Krijanovski, Y. Articles by Schmaier, A. H. Search for Related Content PubMed PubMed Citation Articles by Krijanovski, Y. Articles by Schmaier, A. H. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 June 2003, Vol. 101, No. 11, pp. 4430-4436 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Characterization of molecular defects of Fitzgerald trait and another novel high-molecular-weight kininogen-deficient patient: insights into structural requirements for kininogen expression Yelena Krijanovski, Valerie Proulle, Fakhri Mahdi, Marie Dreyfus, Werner Müller-Esterl, and Alvin H. Schmaier From the Department of Internal Medicine and the Department of Pathology, University of Michigan, Ann Arbor, MI; Hámatologie, Hôpital Bicêtre, AP-HP, Facultá de Mádecine Paris XI, France; and the Department of Biochemistry II, University of Frankfurt, Germany. A 6-year-old male with vertebral-basilar artery thrombosis was recognized to have high-molecular-weight kininogen (HK) deficiency. The propositus had no HK procoagulant activity and antigen (< 1%). Using monoclonal antibodies (Mabs) to kininogen domain 3, the propositus, family members, and Fitzgerald plasma were determined to have detectable low-molecular-weight kininogen. Mabs to HK domains 5 and 6 do not detect HK antigen in the propositus' plasma. The propositus has a single base pair (bp) deletion in cDNA position 1492 of exon 10 affecting amino acid 480 of the mature protein and resulting in a frameshift and a premature stop codon at position 1597 (amino acid 532). Unexpectedly, Mabs to the heavy chain and domain 5 of HK detect a 92-kDa form of HK in Fitzgerald plasma, the first HK-deficient plasma. The 92-kDa Fitzgerald HK has amino acid residues through 502, corresponding to domains 1 through 5, but lacks epitopes of domain 6 (positions 543 to 595). Fitzgerald DNA has a normal exon 10, but a 17-bp mutation in intron 9. These combined results indicate that mutations in the kininogen gene may differentially affect biosynthesis, processing, and/or secretion of HK. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Merkulov, W.-M. Zhang, A. A. Komar, A. H. Schmaier, E. Barnes, Y. Zhou, X. Lu, T. Iwaki, F. J. Castellino, G. Luo, et al. Deletion of murine kininogen gene 1 (mKng1) causes loss of plasma kininogen and delays thrombosis Blood, February 1, 2008; 111(3): 1274 - 1281. [Abstract] [Full Text] [PDF] T. Shigekiyo, J. Miyagi, A. Shirakami, H. Shibata, K. Tsukai, and K.-i. Aihara Isolated high-molecular-weight kininogen deficiency: a novel frameshift mutation in exon 10 Blood, June 1, 2007; 109(11): 5062 - 5063. [Full Text] [PDF] A. Girolami, S. Gavasso, E. Pacquola, L. Cabrio, A. M. Lombardi, and B. Girolami Comparable Levels of Activity and Antigen in Factor XII Deficiency: A Study of 21 Homozygotes and 58 Heterozygotes Clinical and Applied Thrombosis/Hemostasis, July 1, 2005; 11(3): 335 - 338. [Abstract] [PDF]

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