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Blood, 15 July 2005, Vol. 106, No. 2, pp. 542-549. Prepublished online as a Blood First Edition Paper on March 24, 2005; DOI 10.1182/blood-2004-05-2056. This Article Full Text (PDF) All Versions of this Article: 2004-05-2056v1 106/2/542    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 Albrecht, C. Articles by Higgins, C. F Search for Related Content PubMed PubMed Citation Articles by Albrecht, C. Articles by Higgins, C. F Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 2, 2004 Accepted February 15, 2005 A novel missense mutation in ABCA1 results in altered protein trafficking and reduced phosphatidylserine translocation in a patient with Scott syndrome Christiane Albrecht*, John H McVey, James I Elliott, Alessandro Sardini, Ildiko Kasza, Andrew D Mumford, Rossi P Naoumova, Edward G Tuddenham, Katalin Szabo, and Christopher F Higgins MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, Hammersmith Hospital Campus, London, United Kingdom; Physiology Weihenstephan, Technical University Munich, Freising, Germany MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, Hammersmith Hospital Campus, London, United Kingdom National Medical Center, Institute of Haematology and Immunology, Research Group of the Hungarian Academy of Sciences, Budapest, Hungary Hungarian Academy of Sciences, Institute of Enzymology, Budapest, Hungary * Corresponding author; email: Christiane.Albrecht{at}wzw.tum.de. Scott syndrome (SS) is a bleeding disorder characterised by a failure to expose phosphatidylserine (PS) to the outer leaflet of the platelet plasma membrane. As the ATP-binding cassette transporter A1 (ABCA1) is implicated in the exofacial translocation of PS, we assessed its role in the pathophysiology of a patient with SS. Substantially reduced levels of ABCA1 mRNA were found in the patient's leucocytes, compared with controls. The SS patient was heterozygous for a novel missense mutation c.6064G >A (ABCA1 R1925Q), absent from unaffected family members and controls. Both mutant and wild-type alleles were reduced in mRNA expression, and no causative mutation for this phenomenon was identified in the ABCA1 gene or its proximal promoter, suggesting a putative second mutation in a trans-acting regulatory gene may also be involved in the disorder within this patient. In vitro expression studies showed impaired trafficking of ABCA1 R1925Q to the plasma membrane. Overexpression of wild-type ABCA1 in SS lymphocytes complemented the Ca2+-dependent PS exposure at the cell surface. These data identify a mutation in ABCA1 that contributes to the defective PS translocation phenotype in our SS patient. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: An ABC for Scott syndrome? Florence Toti and Jean-Marie Freyssinet Blood 2005 106: 396-397. [Full Text] [PDF] This article has been cited by other articles: M. Fukuda, M. Nakano, M. Miyazaki, M. Tanaka, H. Saito, S. Kobayashi, M. Ueno, and T. Handa Conformational change of apolipoprotein A-I and HDL formation from model membranes under intracellular acidic conditions J. Lipid Res., November 1, 2008; 49(11): 2419 - 2426. [Abstract] [Full Text] [PDF] Y. Cheli, D. Jensen, P. Marchese, D. Habart, T. Wiltshire, M. Cooke, J. A. Fernandez, J. Ware, Z. M. Ruggeri, and T. J. 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