{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T22:55:26Z","timestamp":1788648926651,"version":"build-2803163510"},"reference-count":21,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T00:00:00Z","timestamp":1724716800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T00:00:00Z","timestamp":1724716800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003243","name":"Ministerstvo Zdravotnictv\u00ed Cesk\u00e9 Republiky","doi-asserted-by":"publisher","award":["NU20\u201008\u201000137"],"award-info":[{"award-number":["NU20\u201008\u201000137"]}],"id":[{"id":"10.13039\/501100003243","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010653","name":"Masarykova Univerzita","doi-asserted-by":"publisher","award":["MUNI\/A\/1224\/2022"],"award-info":[{"award-number":["MUNI\/A\/1224\/2022"]}],"id":[{"id":"10.13039\/501100010653","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010653","name":"Masarykova Univerzita","doi-asserted-by":"publisher","award":["MUNI\/11\/SUP\/22\/2020"],"award-info":[{"award-number":["MUNI\/11\/SUP\/22\/2020"]}],"id":[{"id":"10.13039\/501100010653","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["CZ.02.1.01\/0.0\/0.0\/16_026\/0008448"],"award-info":[{"award-number":["CZ.02.1.01\/0.0\/0.0\/16_026\/0008448"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    The\n                    <jats:italic>CYCS<\/jats:italic>\n                    gene is highly evolutionarily conserved, with only a few pathogenic variants that cause thrombocytopenia\u20104 (THC4). Here, we report a novel\n                    <jats:italic>CYCS<\/jats:italic>\n                    variant NM_018947.6: c.59C&gt;T [NP_061820.1:p.(Thr20Ile)] segregating with thrombocytopenia in three generations of a Czech family. The phenotype of the patients corresponds to THC4 with platelets of normal size and morphology and dominant inheritance. Intriguingly, a gradual decline in platelet counts was observed across generations. CRISPR\/Cas9\u2010mediated gene editing was used to introduce the new\n                    <jats:italic>CYCS<\/jats:italic>\n                    gene variant into a megakaryoblast cell line (MEG\u201001). Subsequently, the adhesion, shape, size, ploidy, viability, mitochondrial respiration, cytochrome c protein (CYCS) expression, cell surface antigen expression and caspase activity were analysed in cells carrying the studied variant. Interestingly, the variant decreases the expression of CYCS while increasing mitochondrial respiration and the expression of CD9 cell surface antigen. Surprisingly, the variant abates caspase activation, contrasting with previously known effects of other\n                    <jats:italic>CYCS<\/jats:italic>\n                    variants. Some reports indicate that caspases may be involved in thrombopoiesis; thus, the observed dysregulation of caspase activity might contribute to thrombocytopenia. The findings significantly enhance our understanding of the molecular mechanisms underlying inherited thrombocytopenia and may have implications for diagnosis, prognosis and future targeted therapies.\n                  <\/jats:p>","DOI":"10.1111\/bjh.19694","type":"journal-article","created":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T21:05:10Z","timestamp":1724792710000},"page":"2450-2458","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A novel thrombocytopenia\u20104\u2010causing\n                    <scp>CYCS<\/scp>\n                    gene variant decreases caspase activity: Three\u2010generation study"],"prefix":"10.1111","volume":"205","author":[{"given":"Ji\u0159\u00ed","family":"\u0160tika","sequence":"first","affiliation":[{"name":"Center of Molecular Medicine CEITEC \u2013 Central European Institute of Technology, Masaryk University  Brno Czechia"},{"name":"Institute of Medical Genetics and Genomics Faculty of Medicine, Masaryk University and University Hospital Brno  Brno Czechia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Pe\u0161ov\u00e1","sequence":"additional","affiliation":[{"name":"Center of Molecular Medicine CEITEC \u2013 Central European Institute of Technology, Masaryk University  Brno Czechia"},{"name":"Department of Internal Medicine \u2013 Hematology and Oncology Faculty of Medicine, Masaryk University and University Hospital Brno  Brno Czechia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate\u0159ina Sta\u0148o","family":"Kozub\u00edk","sequence":"additional","affiliation":[{"name":"Center of Molecular Medicine CEITEC \u2013 Central European Institute of Technology, Masaryk University  Brno Czechia"},{"name":"Institute of Medical Genetics and Genomics Faculty of Medicine, Masaryk University and University Hospital Brno  Brno Czechia"},{"name":"Department of Internal Medicine \u2013 Hematology and Oncology Faculty of Medicine, Masaryk University and University Hospital Brno  Brno Czechia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Skaln\u00edkov\u00e1","sequence":"additional","affiliation":[{"name":"Center of Molecular Medicine CEITEC \u2013 Central European Institute of Technology, Masaryk University  Brno Czechia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lenka","family":"Dost\u00e1lov\u00e1","sequence":"additional","affiliation":[{"name":"Center of Molecular Medicine CEITEC \u2013 Central European Institute of Technology, Masaryk University  Brno Czechia"},{"name":"Department of Biology Faculty of Medicine, Masaryk University  Brno Czechia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom\u00e1\u0161","family":"Loja","sequence":"additional","affiliation":[{"name":"Center of Molecular Medicine CEITEC \u2013 Central European Institute of Technology, Masaryk University  Brno Czechia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lenka","family":"Radov\u00e1","sequence":"additional","affiliation":[{"name":"Center of Molecular Medicine CEITEC \u2013 Central European Institute of Technology, Masaryk University  Brno Czechia"},{"name":"Institute of Medical Genetics and Genomics Faculty of Medicine, Masaryk University and University Hospital Brno  Brno Czechia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Palu\u0161ov\u00e1","sequence":"additional","affiliation":[{"name":"Center of Molecular Medicine CEITEC \u2013 Central European Institute of Technology, Masaryk University  Brno Czechia"},{"name":"International Clinical Research Center St. Anne's University Hospital  Brno Czechia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamila","family":"R\u00e9blov\u00e1","sequence":"additional","affiliation":[{"name":"Center of Molecular Medicine CEITEC \u2013 Central European Institute of Technology, Masaryk University  Brno Czechia"},{"name":"Institute of Medical Genetics and Genomics Faculty of Medicine, Masaryk University and University Hospital Brno  Brno Czechia"},{"name":"Department of Internal Medicine \u2013 Hematology and Oncology Faculty of Medicine, Masaryk University and University Hospital Brno  Brno Czechia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuzana","family":"Vrzalov\u00e1","sequence":"additional","affiliation":[{"name":"Center of Molecular Medicine CEITEC \u2013 Central European Institute of Technology, Masaryk University  Brno Czechia"},{"name":"Institute of Medical Genetics and Genomics Faculty of Medicine, Masaryk University and University Hospital Brno  Brno Czechia"},{"name":"Department of Internal Medicine \u2013 Hematology and Oncology Faculty of Medicine, Masaryk University and University Hospital Brno  Brno Czechia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivona","family":"Blah\u00e1kov\u00e1","sequence":"additional","affiliation":[{"name":"Center of Molecular Medicine CEITEC \u2013 Central European Institute of Technology, Masaryk University  Brno Czechia"},{"name":"Institute of Medical Genetics and Genomics Faculty of Medicine, Masaryk University and University Hospital Brno  Brno Czechia"},{"name":"Department of Internal Medicine \u2013 Hematology and Oncology Faculty of Medicine, Masaryk University and University Hospital Brno  Brno Czechia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakub","family":"Trizuljak","sequence":"additional","affiliation":[{"name":"Center of Molecular Medicine CEITEC \u2013 Central European Institute of Technology, Masaryk University  Brno Czechia"},{"name":"Institute of Medical Genetics and Genomics Faculty of Medicine, Masaryk University and University Hospital Brno  Brno Czechia"},{"name":"Department of Internal Medicine \u2013 Hematology and Oncology Faculty of Medicine, Masaryk University and University Hospital Brno  Brno Czechia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stjepan","family":"Uldrijan","sequence":"additional","affiliation":[{"name":"Department of Biology Faculty of Medicine, Masaryk University  Brno Czechia"},{"name":"International Clinical Research Center St. Anne's University Hospital  Brno Czechia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Blatn\u00fd","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Genomics Faculty of Medicine, Masaryk University and University Hospital Brno  Brno Czechia"},{"name":"Department of Pediatric Hematology and Biochemistry University Hospital Brno  Brno Czechia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"\u0160m\u00edda","sequence":"additional","affiliation":[{"name":"Center of Molecular Medicine CEITEC \u2013 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