A dominant-negative GFI1B mutation in the gray platelet syndrome

N Engl J Med. 2014 Jan 16;370(3):245-53. doi: 10.1056/NEJMoa1308130. Epub 2013 Dec 10.


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.

MeSH terms

  • Blood Platelets / pathology*
  • Bone Marrow / pathology
  • Female
  • Genes, Dominant
  • Gray Platelet Syndrome / genetics*
  • Gray Platelet Syndrome / pathology
  • Humans
  • Male
  • Megakaryocytes / pathology*
  • Mutation*
  • Pedigree
  • Proto-Oncogene Proteins / genetics*
  • Repressor Proteins / genetics*
  • Stem Cells
  • Thrombocytopenia / genetics


  • GFI1B protein, human
  • Proto-Oncogene Proteins
  • Repressor Proteins