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Blood, 8 January 2009, Vol. 113, No. 2, pp. 458-461. Prepublished online as a Blood First Edition Paper on October 10, 2008; DOI 10.1182/blood-2008-06-162610. This Article Full Text Full Text (PDF) Supplemental Tables and Figure All Versions of this Article: blood-2008-06-162610v1 113/2/458    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 Kunishima, S. Articles by Saito, H. Search for Related Content PubMed PubMed Citation Articles by Kunishima, S. Articles by Saito, H. Related Collections Hemostasis, Thrombosis, and Vascular Biology Platelets and Thrombopoiesis Brief Reports Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PLATELETS AND THROMBOPOIESIS Brief Report Mutation of the β1-tubulin gene associated with congenital macrothrombocytopenia affecting microtubule assembly Shinji Kunishima1, Ryoji Kobayashi2, Tomohiko J. Itoh3, Motohiro Hamaguchi1, and Hidehiko Saito4 1 Department of Hemostasis and Thrombosis, Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan; 2 Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan; 3 Division of Biological Sciences, Graduate School of Science, Nagoya University, Nagoya, Japan; and 4 Nagoya Central Hospital, Nagoya, Japan Congenital macrothrombocytopenia is a genetically heterogeneous group of rare disorders. We identified the first TUBB1 mutation, R318W, in a patient with congenital macrothrombocytopenia. The patient was heterozygous for Q43P, but this single-nucleotide polymorphism (SNP) did not relate to macrothrombocytopenia. Although no abnormal platelet β1-tubulin localization/marginal band organization was observed, the level of β1-tubulin was decreased by approximately 50% compared with healthy controls. Large and irregular bleb protrusions observed in megakaryocytes derived from the patient's peripheral blood CD34+ cells suggested impaired megakaryocyte fragmentation and release of large platelets. In vitro transfection experiments in Chinese hamster ovary (CHO) cells demonstrated no incorporation of mutant β1-tubulin into microtubules, but the formation of punctuated insoluble aggregates. These results suggested that mutant protein is prone to aggregation but is unstable within megakaryocytes/platelets. Alternatively, mutant β1-tubulin may not be transported from the megakaryocytes into platelets. W318 β1-tubulin may interfere with normal platelet production, resulting in macrothrombocytopenia. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: β1-tubulin gene mutation platelets are not macrothrombocytes James G. White Blood 2009 114: 492. [Full Text] [PDF] Response:W318 β1-tubulin and macrothrombocytopenia Shinji Kunishima and Hidehiko Saito Blood 2009 114: 492-493. [Full Text] [PDF] Hereditary hemochromatosis due to resistance to hepcidin: high hepcidin concentrations in a family with C326S ferroportin mutation Ronald L. Sham, Pradyumna D. Phatak, Elizabeta Nemeth, and Tomas Ganz Blood 2009 114: 493-494. [Full Text] [PDF] This article has been cited by other articles: J. G. White {beta}1-tubulin gene mutation platelets are not macrothrombocytes Blood, July 9, 2009; 114(2): 492 - 492. [Full Text] [PDF] S. Kunishima and H. Saito Response:W318 {beta}1-tubulin and macrothrombocytopenia Blood, July 9, 2009; 114(2): 492 - 493. [Full Text] [PDF] A. E. Geddis The regulation of proplatelet production Haematologica, June 1, 2009; 94(6): 756 - 759. [Full Text] [PDF]

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