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Various etiologies of thrombocytopenia, including genetic, immunological, and hematopoietic abnormalities, determine the prognosis for this disease. In this study, we identified a novel heterozygous mutation in a gene encoding cytochrome c, somatic (<jats:italic>CYCS<\/jats:italic>, MIM123970) using whole exome sequencing. This variant (c.301_303del:p.Lys101del) is located in the \u03b1\u2010helix of the cytochrome c (CYCS) C\u2010terminal domain. <jats:italic>In silico<\/jats:italic> structural analysis suggested that this mutation results in protein folding instability. CYCS is one of the key factors regulating the intrinsic apoptotic pathway and the mitochondrial respiratory chain. Using the yeast model system, we clearly demonstrated that this one amino acid deletion (in\u2010frame) resulted in significantly reduced cytochrome c protein expression and functional defects in the mitochondrial respiratory chain, indicating that the loss of function of cytochrome c underlies thrombocytopenia. The clinical features of known <jats:italic>CYCS<\/jats:italic> variants have been reported to be confined to mild or asymptomatic thrombocytopenia, as was observed for the patient in our study. This study clearly demonstrates that thrombocytopenia can result from <jats:italic>CYCS<\/jats:italic> loss\u2010of\u2010function variants.<\/jats:p>","DOI":"10.1111\/cge.13423","type":"journal-article","created":{"date-parts":[[2018,7,27]],"date-time":"2018-07-27T06:08:48Z","timestamp":1532671728000},"page":"548-553","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["A novel <i>CYCS<\/i> mutation in the \u03b1\u2010helix of the CYCS C\u2010terminal domain causes non\u2010syndromic thrombocytopenia"],"prefix":"10.1111","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4540-5277","authenticated-orcid":false,"given":"Yuri","family":"Uchiyama","sequence":"first","affiliation":[{"name":"Department of Human Genetics Yokohama City University Graduate School of Medicine  Yokohama Japan"},{"name":"Department of Oncology Yokohama City University Graduate School of Medicine  Yokohama 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