CYCS-related thrombocytopenia in three Japanese families with a novel variant in one family
Natsuhiko Yamada1, Atsushi Sakamoto2,3, Rintaro Nagoshi1,4
1Center for Postgraduate Education and Training, National Center for Child Health and Development (NCCHD), Tokyo, Japan.
Insights
Genetic variants in the CYCS gene cause autosomal dominant, non-syndromic thrombocytopenia. This condition affects platelet counts without other blood cell abnormalities, suggesting CYCS as a key gene for familial thrombocytopenia.
Area of Science:
- Genetics
- Hematology
- Molecular Biology
Background:
- Somatic cytochrome c (CYCS) is crucial for cellular respiration.
- Thrombocytopenia, a condition of low platelet count, can be congenital and familial.
- Understanding the genetic basis of inherited thrombocytopenia is vital for diagnosis and management.
Purpose of the Study:
- To investigate the genetic cause of autosomal dominant, non-syndromic thrombocytopenia in three Japanese families.
- To identify pathogenic variants in the CYCS gene associated with familial thrombocytopenia.
Main Methods:
- Targeted gene sequencing was performed on patients with unexplained familial thrombocytopenia.
- Analysis focused on identifying mutations within the CYCS gene.
- Segregation analysis within families confirmed the inheritance pattern of identified variants.
Main Results:
- Nine cases of autosomal dominant, non-syndromic CYCS-related thrombocytopenia were identified across three families.
- Patients exhibited mild or no bleeding tendencies, with normal platelet size and morphology.
- Pathogenic missense variants in CYCS, including two previously reported and one novel variant (c.212A>C, p.(Asn71Thr)), were found in affected individuals.
Conclusions:
- Pathogenic variants in the CYCS gene are a cause of autosomal dominant, non-syndromic thrombocytopenia.
- CYCS-related thrombocytopenia presents with isolated low platelet counts and minimal bleeding.
- Genetic testing for CYCS variants should be considered for unexplained familial thrombocytopenia.
Abstract:
CYCS encodes somatic cytochrome c, which plays a central role in the electron transport chain and oxidative phosphorylation. We report nine cases of autosomal dominant, non-syndromic CYCS-related thrombocytopenia in three Japanese families. Patients showed no or mild bleeding tendency, with preserved platelet size and morphology, and without other abnormalities in blood cell lineages. Using targeted gene sequencing for congenital thrombocytopenia, we identified pathogenic missense variants in CYCS, shared by all affected individuals in each family. Two were previously reported: c.274A > G,p.(Arg92Gly) and c.309C > T,p.(Thr103Ile); one was novel: c.212A > C,p.(Asn71Thr). Genetic testing should be considered in unexplained familial thrombocytopenia.
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