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Blood, 1 February 2008, Vol. 111, No. 3, pp. 1299-1301. Prepublished online as a Blood First Edition Paper on October 30, 2007; DOI 10.1182/blood-2007-09-112854. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-09-112854v1 111/3/1299    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 Nyfeler, B. Articles by Neerman-Arbez, M. Search for Related Content PubMed PubMed Citation Articles by Nyfeler, B. Articles by Neerman-Arbez, M. Related Collections Brief Reports Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Brief Report Deletion of 3 residues from the C-terminus of MCFD2 affects binding to ERGIC-53 and causes combined factor V and factor VIII deficiency Beat Nyfeler1, Yukiko Kamiya2, Françoise Boehlen3, Kazuo Yamamoto4, Koichi Kato2,5, Philippe de Moerloose3, Hans-Peter Hauri1, and Marguerite Neerman-Arbez3,6 1 Biozentrum, University of Basel, Basel, Switzerland; 2 Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan; 3 Division of Angiology and Hemostasis, University Hospitals, Geneva, Switzerland; 4 Graduate School of Frontier Sciences, University of Tokyo, Chiba, Japan; 5 Institute for Molecular Science, National Institutes of Natural Sciences, Okazaki, Japan; and 6 Department of Genetic Medicine and Development, University Medical School, Geneva, Switzerland Combined factor V and factor VIII deficiency (F5F8D) is a rare, autosomal recessive coagulation disorder. F5F8D is genetically linked to mutations in the transmembrane lectin ERGIC-53 and its soluble interaction partner MCFD2. The ERGIC-53/MCFD2 protein complex functions as transport receptor of coagulation factors V and VIII by mediating their export from the endoplasmic reticulum (ER). Here, we studied a F5F8D patient who was found to be a compound heterozygote for 2 novel mutations in MCFD2: a large deletion of 8.4 kb eliminating the 5'UTR of the gene and a nonsense mutation resulting in the deletion of only 3 amino acids (SLQ) from the C-terminus of MCFD2. Biochemical and structural analysis of the SLQ mutant demonstrated impaired binding to ERGIC-53 due to modification of the 3-dimensional structure of MCFD2. Our results highlight the importance of the ERGIC-53/MCFD2 protein interaction for the efficient secretion of coagulation factors V and VIII. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. Zhang, M. Spreafico, C. Zheng, A. Yang, P. Platzer, M. U. Callaghan, Z. Avci, N. Ozbek, J. Mahlangu, T. Haw, et al. Genotype-phenotype correlation in combined deficiency of factor V and factor VIII Blood, June 15, 2008; 111(12): 5592 - 5600. [Abstract] [Full Text] [PDF] B. Nyfeler, V. Reiterer, M. W. Wendeler, E. Stefan, B. Zhang, S. W. Michnick, and H.-P. Hauri Identification of ERGIC-53 as an intracellular transport receptor of {alpha}1-antitrypsin J. Cell Biol., February 25, 2008; 180(4): 705 - 712. [Abstract] [Full Text] [PDF]

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