학술논문
A Dominant-Negative GFI1B Mutation in the Gray Platelet Syndrome
Document Type
Academic Journal
Author
Monteferrario, Davide; Bolar, Nikhita A.; Marneth, Anna E.; Hebeda, Konnie M.; Bergevoet, Saskia M.; Veenstra, Hans; Laros-van Gorkom, Britta A.P.; MacKenzie, Marius A.; Khandanpour, Cyrus; Botezatu, Lacramiora; Fransen, Erik; Van Camp, Guy; Duijnhouwer, Anthonie L.; Salemink, Simone; Willemsen, Brigith; Huls, Gerwin; Preijers, Frank; Van Heerde, Waander; Jansen, Joop H.; Kempers, Marlies J.E.; Loeys, Bart L.; Van Laer, Lut; Van der Reijden, Bert A.
Source
The New England Journal of Medicine. Jan 16, 2014 370(3):245-253
Subject
Language
English
ISSN
0028-4793
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.