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.