title: Mutations of cytochrome c identified in patients with thrombocytopenia THC4 affect both apoptosis and cellular bioenergetics.
abstract: 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.
authors: Department of Medical Sciences, University of Trieste, Trieste, Italy.
authors: Daniela
authors: D
authors: De Rocco
authors: Clinical Genetics Unit, Dept. of Woman and Child Health, University of Padova, IRP Città della Speranza, Padova, Italy.
authors: Cristina
authors: C
authors: Cerqua
authors: Department of Life Sciences, University of Parma, Parma, Italy.
authors: Paola
authors: P
authors: Goffrini
authors: Division of Pediatric Hematology/Oncology, University of Catania, Catania, Italy.
authors: Giovanna
authors: G
authors: Russo
authors: National Institute for Medical Research, London, NW71AA, UK.
authors: Annalisa
authors: A
authors: Pastore
authors: Department of Life Sciences, University of Parma, Parma, Italy.
authors: Francesca
authors: F
authors: Meloni
authors: Department of Medical Sciences, University of Trieste, Trieste, Italy.
authors: Elena
authors: E
authors: Nicchia
authors: Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA.
authors: Carlos T
authors: CT
authors: Moraes
authors: Department of Internal Medicine, University of Pavia-IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
authors: Alessandro
authors: A
authors: Pecci
authors: Clinical Genetics Unit, Dept. of Woman and Child Health, University of Padova, IRP Città della Speranza, Padova, Italy.
authors: Leonardo
authors: L
authors: Salviati
authors: Department of Medical Sciences, University of Trieste, Trieste, Italy; Institute for Maternal and Child Health-IRCCS Burlo Garofolo, Trieste, Italy. Electronic address: anna.savoia@burlo.trieste.it.
authors: Anna
authors: A
authors: Savoia
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D002478:Cells, Cultured; D002675:Child, Preschool; D045304:Cytochromes c / Q000235:genetics*; D004252:DNA Mutational Analysis; D004622:Embryo, Mammalian / Q000166:cytology; D004734:Energy Metabolism / Q000235:genetics*; D005192:Family Health; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000166:cytology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010101:Oxygen Consumption / Q000235:genetics; D010375:Pedigree; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013921:Thrombocytopenia / Q000235:genetics* / Q000473:pathology
chemical_list: D045304:Cytochromes c
keywords: Apoptosis; Cellular bioenergetics; Cytochrome c; Thrombocytopenia THC4