Semin Thromb Hemost 2011; 37(6): 664-672
DOI: 10.1055/s-0031-1291376
© Thieme Medical Publishers

Congenital Thrombocytopenia and Cytochrome c Mutation: A Matter of Birth and Death

Elisabeth Cramer Bordé1 , Yasmine Ouzegdouh1 , Elizabeth C. Ledgerwood2 , Ian M. Morison3
  • 1Department of Hematology, University of Versailles-St Quentin, Institut Cochin, Paris, France
  • 2Department of Biochemistry, University of Otago Dunedin, University of Otago Dunedin, New Zealand
  • 3Department of Pathology, Dunedin School of Medicine, University of Otago Dunedin, New Zealand
Further Information

Publication History

Publication Date:
18 November 2011 (online)

Abstract

Thrombocytopenia (TP) Cargeeg is a unique autosomal dominant disorder, affecting a seven-generation family, caused by cytochrome c (CYCS) mutation that dysregulates platelet formation. The CYCS mutation in this disorder is a glycine 41 replacement by serine, which yields a cytochrome c variant with enhanced apoptotic pathway activity in vitro. The deregulated apoptosis in this disorder affects megakaryocytes (MK) during platelet formation, leading to early and ectopic platelet release in the bone marrow (BM). Notably, the family has no other phenotypic indication of abnormal apoptosis, implying that cytochrome c activity is not a critical regulator of physiological apoptosis in most cells. The pathophysiology of this unique inherited TP, with unaltered platelet survival and normal MK content in the BM, has implications for physiological and pathological mechanisms altering MK apoptosis, with implications for other unexplained thrombocytopenic disorders.

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Elisabeth Cramer BordéM.D. Ph.D. 

Professor, Service d'hématologie et d'immunologie, Hôpital Ambroise Paré

9 Avenue Charles de Gaulle, 92100 Boulogne-Billancourt, France

Email: elisabeth.borde@apr.aphp.fr