A Dominant-Negative GFI1B Mutation in the Gray Platelet Syndrome

• Published in: The New England journal of medicine Vol. 370; no. 3; pp. 245 - 253
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 16.01.2014
• Series: Brief Report
• Subjects: Biological and medical sciences; Blood diseases; Blood Platelets - pathology; Bone marrow; Bone Marrow - pathology; Female; General aspects; Genes; Genes, Dominant; Gray Platelet Syndrome - genetics; Gray Platelet Syndrome - pathology; Hereditary diseases; Humans; Male; Medical sciences; Megakaryocytes; Megakaryocytes - pathology; Mutation; Nonsense mutation; Pedigree; Platelets; Proto-Oncogene Proteins - genetics; Repressor Proteins - genetics; Stem Cells; Thrombocytopenia - genetics; Medicine; Platelet; Mutation
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa1308130

A large family is described with gray platelet syndrome due to an autosomal dominant inheritance pattern related to a dominant-negative mutation in GFI1B . The mutation leads to a loss in gene repression during megakaryocyte development. Platelets are formed through fragmentation of megakaryocytes that reside in the bone marrow. 1 , 2 Platelet alpha granules, which are by far the most abundant platelet organelles, store proteins that stimulate platelet adhesiveness, hemostasis, and wound healing. 3 , 4 The gray platelet syndrome is an inherited bleeding disorder characterized by defective production of alpha granules. 5 , 6 Patients with this syndrome have reduced numbers of larger-than-normal platelets, and on light microscopy these platelets have a typical gray appearance caused by the lack of alpha granules. For a final diagnosis, the lack of alpha granules must be confirmed by means of electron microscopy. 7 Clinically, . . .