• Davide Monteferrario, Nikhita A Bolar, Anna E Marneth, Konnie M Hebeda, Saskia M Bergevoet, Hans Veenstra, Britta A P Laros-van Gorkom, Marius A MacKenzie, Cyrus Khandanpour, Lacramiora Botezatu, Erik Fransen, Guy Van Camp, Anthonie L Duijnhouwer, Simone Salemink, Brigith Willemsen, Gerwin Huls, Frank Preijers, Waander Van Heerde, Joop H Jansen, Marlies J E Kempers, Bart L Loeys, Lut Van Laer, and Bert A Van der Reijden.
• From the Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen Center for Molecular Life Sciences (D.M., A.E.M., S.M.B., H.V., G.H., F.P., W.V.H., J.H.J., B.A.V.R.) and the Departments of Pathology (K.M.H., B.W.), Hematology (B.A.P.L.G., M.A.M., G.H.), Cardiology (A.L.D.), and Human Genetics (S.S., M.J.E.K.), Radboud University Medical Center - all in Nijmegen, the Netherlands; the Department of Medical Genetics, Antwerp University Hospital and University of Antwerp (N.A.B., E.F., G.V.C., B.L.L., L.V.L.) and the Statua Center for Statistics, University of Antwerp (E.F.), Antwerp, Belgium; and the Department of Hematology, University Hospital, Essen, Germany (C.K., L.B.).
• N. Engl. J. Med.. 2014 Jan 16;370(3):245-53.

AbstractThe gray platelet syndrome is a hereditary, usually autosomal recessive bleeding disorder caused by a deficiency of alpha granules in platelets. We detected a nonsense mutation in the gene encoding the transcription factor GFI1B (growth factor independent 1B) that causes autosomal dominant gray platelet syndrome. Both gray platelets and megakaryocytes had abnormal marker expression. In addition, the megakaryocytes had dysplastic features, and they were abnormally distributed in the bone marrow. The GFI1B mutant protein inhibited nonmutant GFI1B transcriptional activity in a dominant-negative manner. Our studies show that GFI1B, in addition to being causally related to the gray platelet syndrome, is key to megakaryocyte and platelet development.

23 keywords...

hide…