Brief Communication abstract
Nature Genetics 40, 387 - 389 (2008)
Published online: 16 March 2008 | doi:10.1038/ng.103
A mutation of human cytochrome c enhances the intrinsic apoptotic pathway but causes only thrombocytopenia
Ian M Morison1, Elisabeth M Cramer Bordé2,3, Emma J Cheesman1, Pak Leng Cheong1, Andrew J Holyoake4, Serge Fichelson3,5, Robert J Weeks1, Alexandra Lo1, Stefan M K Davies1, Sigurd M Wilbanks1, Robert D Fagerlund1, Mathew W Ludgate1, Fernanda M da Silva Tatley1, Melanie S A Coker1, Nicholas A Bockett1, Gillian Hughes1, Diana A Pippig1, Mark P Smith6, Claude Capron2,3 & Elizabeth C Ledgerwood1
We report the first identified mutation in the gene encoding human cytochrome c (CYCS). Glycine 41, invariant throughout eukaryotes, is substituted by serine in a family with autosomal dominant thrombocytopenia caused by dysregulated platelet formation. The mutation yields a cytochrome c variant with enhanced apoptotic activity in vitro. Notably, the family has no other phenotypic indication of abnormal apoptosis, implying that cytochrome c activity is not a critical regulator of most physiological apoptosis.
- Department of Biochemistry, University of Otago, PO Box 56, Dunedin 9054, New Zealand.
- Faculté de Médecine Paris-Ilede France-Ouest, Université de Versailles Saint Quentin, France.
- Institut Cochin, INSERM, U567, Maternité Port-Royal, 123 Bd de Port-Royal, 75014 Paris, France.
- Pacific Edge Biotechnology Ltd, PO Box 56, Dunedin 9054, New Zealand.
- Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), INSERM U567, Paris, France.
- Canterbury District Health Board, Private Bag 4710, Christchurch 8140, New Zealand.
Correspondence to: Ian M Morison1 e-mail: ian.morison@otago.ac.nz
