TY - JOUR T1 - Mutations of cytochrome c identified in patients with thrombocytopenia THC4 affect both apoptosis and cellular bioenergetics. JF - Biochim Biophys Acta Y1 - 2014 A1 - De Rocco, Daniela A1 - Cerqua, Cristina A1 - Goffrini, Paola A1 - Russo, Giovanna A1 - Pastore, Annalisa A1 - Meloni, Francesca A1 - Nicchia, Elena A1 - Moraes, Carlos T A1 - Pecci, Alessandro A1 - Salviati, Leonardo A1 - Savoia, Anna KW - Amino Acid Sequence KW - Animals KW - Apoptosis KW - Base Sequence KW - Cells, Cultured KW - Child, Preschool KW - Cytochromes c KW - DNA Mutational Analysis KW - Embryo, Mammalian KW - Energy Metabolism KW - Family Health KW - Female KW - Fibroblasts KW - Humans KW - Lung KW - Male KW - Mice KW - Molecular Sequence Data KW - Mutation, Missense KW - Oxygen Consumption KW - Pedigree KW - Saccharomyces cerevisiae KW - Sequence Homology, Amino Acid KW - Thrombocytopenia AB -

Inherited thrombocytopenias are heterogeneous diseases caused by at least 20 genes playing different role in the processes of megakaryopoiesis and platelet production. Some forms, such as thrombocytopenia 4 (THC4), are very rare and not well characterized. THC4 is an autosomal dominant mild thrombocytopenia described in only one large family from New Zealand and due to a mutation (G41S) of the somatic isoform of the cytochrome c (CYCS) gene. We report a novel CYCS mutation (Y48H) in patients from an Italian family. Similar to individuals carrying G41S, they have platelets of normal size and morphology, which are only partially reduced in number, but no prolonged bleeding episodes. In order to determine the pathogenetic consequences of Y48H, we studied the effects of the two CYCS mutations in yeast and mouse cellular models. In both cases, we found reduction of respiratory level and increased apoptotic rate, supporting the pathogenetic role of CYCS in thrombocytopenia.

VL - 1842 IS - 2 U1 - http://www.ncbi.nlm.nih.gov/pubmed/24326104?dopt=Abstract ER -