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Prepublished online as a Blood First Edition Paper on March 20, 2003; DOI 10.1182/blood-2002-09-2783. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-09-2783v1 102/2/529    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 Deutsch, S. Articles by Beris, P. Search for Related Content PubMed PubMed Citation Articles by Deutsch, S. Articles by Beris, P. Related Collections Gene Expression Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 July 2003, Vol. 102, No. 2, pp. 529-534 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Asp1424Asn MYH9 mutation results in an unstable protein responsible for the phenotypes in May-Hegglin anomaly/Fechtner syndrome Samuel Deutsch, Alexandra Rideau, Marie-Luce Bochaton-Piallat, Giuseppe Merla, Antoine Geinoz, Giulio Gabbiani, Torsten Schwede, Thomas Matthes, Stylianos E. Antonarakis, and Photis Beris From the Division of Medical Genetics, Faculty of Medicine, University of Geneva; Division of Hematology, Geneva University Hospital; Department of Pathology, Faculty of Medicine, University of Geneva; Biozentrum der Universität Basel and Swiss Institute of Bioinformatics; and Graduate Program of Molecular and Cellular Biology, Faculty of Medicine, University of Geneva, Switzerland. May-Hegglin anomaly (MHA), Fechtner syndrome (FTNS), Sebastian syndrome (SBS), and Epstein syndrome (EPS) are a group of rare, autosomal dominant disorders characterized by thrombocytopenia, giant platelets, and Döhle-like inclusion bodies, together with variable manifestations of Alport-like symptoms that include high-tone sensorineural deafness, cataracts, and nephritis. These disorders result from mutations in the MYH9 gene, which encodes for the nonmuscle myosin heavy chain A protein (also known as NMMHC-A). To date 20 different mutations have been characterized for this gene, but no clear phenotype-genotype correlation has been established, and very little is known regarding the molecular pathogenesis of this group of diseases. Here, we describe 2 new families with MHA/FTNS phenotypes that have been characterized in terms of their mutations, protein localization in megakaryocytes, protein expression, and mRNA stability. Our findings suggest that, at least for the Asp1424Asn mutation in the MYH9 gene, the phenotypes result from a highly unstable protein. No abnormalities in protein localization or mRNA stability were observed. We hypothesize that haploinsufficiency of the MYH9 results in a failure to properly reorganize the cytoskeleton in megakaryocytes as required for efficient platelet production. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Kunishima, M. Hamaguchi, and H. Saito Differential expression of wild-type and mutant NMMHC-IIA polypeptides in blood cells suggests cell-specific regulation mechanisms in MYH9 disorders Blood, March 15, 2008; 111(6): 3015 - 3023. [Abstract] [Full Text] [PDF] J. D. Franke, R. A. Montague, W. L. Rickoll, and D. P. Kiehart An MYH9 human disease model in flies: site-directed mutagenesis of the Drosophila non-muscle myosin II results in hypomorphic alleles with dominant character Hum. Mol. Genet., December 15, 2007; 16(24): 3160 - 3173. [Abstract] [Full Text] [PDF] C. Leon, A. Eckly, B. Hechler, B. Aleil, M. Freund, C. Ravanat, M. Jourdain, C. Nonne, J. Weber, R. Tiedt, et al. Megakaryocyte-restricted MYH9 inactivation dramatically affects hemostasis while preserving platelet aggregation and secretion Blood, November 1, 2007; 110(9): 3183 - 3191. [Abstract] [Full Text] [PDF] M. Martinelli, M. Di Stazio, L. Scapoli, J. Marchesini, F. Di Bari, F. Pezzetti, F. Carinci, A. Palmieri, P. Carinci, and A. Savoia Cleft lip with or without cleft palate: implication of the heavy chain of non-muscle myosin IIA J. Med. Genet., June 1, 2007; 44(6): 387 - 392. [Abstract] [Full Text] [PDF] B. Haarer, S. Viggiano, M. A. Hibbs, O. G. Troyanskaya, and D. C. Amberg Modeling complex genetic interactions in a simple eukaryotic genome: actin displays a rich spectrum of complex haploinsufficiencies Genes & Dev., January 15, 2007; 21(2): 148 - 159. [Abstract] [Full Text] [PDF] A. Pecci, I. Canobbio, A. Balduini, L. Stefanini, B. Cisterna, C. Marseglia, P. Noris, A. Savoia, C. L. Balduini, and M. Torti Pathogenetic mechanisms of hematological abnormalities of patients with MYH9 mutations Hum. Mol. Genet., November 1, 2005; 14(21): 3169 - 3178. [Abstract] [Full Text] [PDF] J. D. Franke, F. Dong, W. L. Rickoll, M. J. Kelley, and D. P. Kiehart Rod mutations associated with MYH9-related disorders disrupt nonmuscle myosin-IIA assembly Blood, January 1, 2005; 105(1): 161 - 169. [Abstract] [Full Text] [PDF] S Deutsch, U Choudhury, G Merla, C Howald, A Sylvan, and S E Antonarakis Detection of aneuploidies by paralogous sequence quantification J. Med. Genet., December 1, 2004; 41(12): 908 - 915. [Abstract] [Full Text] [PDF] T. Matthes, P. Aguilar-Martinez, L. Pizzi-Bosman, R. Darbellay, L. Rubbia-Brandt, E. Giostra, M. Michel, T. Ganz, and P. Beris Severe hemochromatosis in a Portuguese family associated with a new mutation in the 5'-UTR of the HAMP gene Blood, October 1, 2004; 104(7): 2181 - 2183. [Abstract] [Full Text] [PDF]

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