title: A dominant-negative GFI1B mutation in the gray platelet syndrome.
abstract: The 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.
authors: 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.).
authors: Davide
authors: D
authors: Monteferrario
authors: Nikhita A
authors: NA
authors: Bolar
authors: Anna E
authors: AE
authors: Marneth
authors: Konnie M
authors: KM
authors: Hebeda
authors: Saskia M
authors: SM
authors: Bergevoet
authors: Hans
authors: H
authors: Veenstra
authors: Britta A P
authors: BA
authors: Laros-van Gorkom
authors: Marius A
authors: MA
authors: MacKenzie
authors: Cyrus
authors: C
authors: Khandanpour
authors: Lacramiora
authors: L
authors: Botezatu
authors: Erik
authors: E
authors: Fransen
authors: Guy
authors: G
authors: Van Camp
authors: Anthonie L
authors: AL
authors: Duijnhouwer
authors: Simone
authors: S
authors: Salemink
authors: Brigith
authors: B
authors: Willemsen
authors: Gerwin
authors: G
authors: Huls
authors: Frank
authors: F
authors: Preijers
authors: Waander
authors: W
authors: Van Heerde
authors: Joop H
authors: JH
authors: Jansen
authors: Marlies J E
authors: MJ
authors: Kempers
authors: Bart L
authors: BL
authors: Loeys
authors: Lut
authors: L
authors: Van Laer
authors: Bert A
authors: BA
authors: Van der Reijden
mesh_terms: D001792:Blood Platelets / Q000473:pathology*; D001853:Bone Marrow / Q000473:pathology; D005260:Female; D005799:Genes, Dominant; D055652:Gray Platelet Syndrome / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008533:Megakaryocytes / Q000473:pathology*; D009154:Mutation; D010375:Pedigree; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D013234:Stem Cells; D013921:Thrombocytopenia / Q000235:genetics
chemical_list: C111977:GFI1B protein, human; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins