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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 19, 2007 Accepted October 29, 2007 Deletion of three residues from the C-terminus of MCFD2 affects binding to ERGIC-53 and causes combined factor V and factor VIII deficiency Beat Nyfeler, Yukiko Kamiya, Francoise Boehlen, Kazuo Yamamoto, Koichi Kato, Philippe de Moerloose, Hans-Peter Hauri, and Marguerite Neerman-Arbez* Biozentrum, University of Basel, Basel, Switzerland Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan Division of Angiology and Hemostasis, University Hospitals, Geneva, Switzerland Graduate School of Frontier Sciences, University of Tokyo, Chiba, Japan Institute for Molecular Science, National Institute of Natural Sciences, Okazaki, Japan Department of Genetic Medicine and Development, University Medical School, Geneva, Switzerland * Corresponding author; email: marguerite.arbez{at}medecine.unige.ch. 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 two 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 three 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 three-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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