A novel thrombocytopenia-4-causing CYCS gene variant decreases caspase activity: Three-generation study
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F24%3A00080344" target="_blank" >RIV/00159816:_____/24:00080344 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14740/24:00137048 RIV/65269705:_____/24:00080344
Result on the web
<a href="https://onlinelibrary.wiley.com/doi/10.1111/bjh.19694" target="_blank" >https://onlinelibrary.wiley.com/doi/10.1111/bjh.19694</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1111/bjh.19694" target="_blank" >10.1111/bjh.19694</a>
Alternative languages
Result language
angličtina
Original language name
A novel thrombocytopenia-4-causing CYCS gene variant decreases caspase activity: Three-generation study
Original language description
The CYCS gene is highly evolutionarily conserved, with only a few pathogenic variants that cause thrombocytopenia-4 (THC4). Here, we report a novel CYCS variant NM_018947.6: c.59C>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-mediated gene editing was used to introduce the new CYCS gene variant into a megakaryoblast cell line (MEG-01). 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 CYCS 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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30205 - Hematology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
British Journal of Haematology
ISSN
0007-1048
e-ISSN
1365-2141
Volume of the periodical
205
Issue of the periodical within the volume
6
Country of publishing house
US - UNITED STATES
Number of pages
9
Pages from-to
2450-2458
UT code for WoS article
001299499800001
EID of the result in the Scopus database
2-s2.0-85202216088