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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 (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 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. Social Bookmarking                   What's this? Submitted September 11, 2002 Accepted March 12, 2003 The D1424N 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, Guilio Gabbiani, Torsten Schwede, Thomas Matthes, Stylianos E Antonarakis, and Photis Beris* Division of Medical Genetics, University of Geneva, Geneva, Switzerland Division of Hematology, Geneva University Hospital, Geneva, Switzerland Department of Pathology, University of Geneva, Geneva, Switzerland Biozentrum, University of Basle & Swiss Institute of Bioinformatics, Basle, Switzerland Graduate Program of Molecular and Cellular Biology, University of Geneva, Geneva, Switzerland * Corresponding author; email: Photis.Beris{at}hcuge.ch. 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 Doehle-like inclusion bodies, together with variable manifestations of Alport-like symptoms which include high tone sensorineural deafness, cataracts and nephritis. These disorders result from mutations in the MYH9 gene, which encodes for the non-muscle 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. In this paper we describe two new families with MHA/FTNS phenotypes which 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 D1424N 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. 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