A Novel Heterozygous Pathogenic Variation in CYCS Gene Cause Autosomal Dominant Non-Syndromic Thrombocytopenia 4 in a Large Chinese Family

Abstract

Aim: To determine the etiology of a Chinese family with thrombocytopenia by analyzing the clinical features and genetic variation.Methods: Clinical profiles and genomic DNA extracts of the family members were collected for the study. Whole exome sequencing and Sanger sequencing was used to detect the associated genetic variation and verify the family co-segregation respectively. Bioinformatics analysis assessed the pathogenicity of missense mutations.Results: The study reported a 3-generation pedigree including eight family members with thrombocytopenia. The platelet counts of the patients were varied, ranging from 38 to 110 × 109/L (reference range: 150–450 x 109/L). The mean volumes and morphology of the sampled platelet were both normal. The bleeding abnormality and mitochondriopathy were not observed in all the patients. Clinical signs of thrombocytopenia were mild. A novel heterozygous missense variant c.79C > T (p.His27Tyr) was identified in CYCS gene associated with autosomal dominant thrombocytopenia.Conclusion: We report the first large family with autosomal dominant non-syndromic thrombocytopenia 4 in a Chinese family, a novel heterozygous missense variant c.79C > T (p.His27Tyr) was identified. The whole exome sequencing is an efficient tool for screening the variants specifically associated with the disease. The finding enriches the mutation spectrum of CYCS gene and laid a foundation for future studies on the correlation between genotype and phenotype.

The Identification and Clinical Value Evaluation of CYCS Related to Asthma through Bioinformatics Analysis and Functional Experiments

“…The binding of CYCS to Apaf-1 triggers the activation of caspase-9, which accelerates cell apoptosis by activating other caspases. Other studies also suggest that mutations in CYCS are associated with autosomal dominant nonsyndromic thrombocytopenia [38]. To investigate the biological properties of CYCS in the pathogenesis of asthma, we examined the expressions of this gene in pancancers using the TCGA and GTEx databases.…”

Evaluating the effects of low-dose simulated galactic cosmic rays on murine hippocampal-dependent cognitive performance

“…The CYCS gene encodes cytochrome c, which functions as a central component of the electron transport chain in mitochondria (Che et al, 2021). PFN1 (profilin 1) is best known to promote and direct actin polymerization (Murk et al, 2021).…”

“…For example, the more intensely green-colored proteins in Figure 7 are CYCS, PFN1, and FAM162A, each representing an upregulated protein with a varying function. The CYCS gene encodes cytochrome c, which functions as a central component of the electron transport chain in mitochondria ( Che et al, 2021 ). PFN1 (profilin 1) is best known to promote and direct actin polymerization ( Murk et al, 2021 ).…”

Thrombocytopenia 4 (THC4): Six novel families with mutations of the cytochrome c gene

“…Although THC4 is the only disease associated with mutations of CYCS known so far, its clinical and molecular features are still poorly characterized, as comprehensive data have been reported only for a few individuals worldwide. [4][5][6][7][8] In this paper, we report two known and three novel heterozygous missense CYCS variants identified in six Italian families. We also describe the clinical and platelet features of a cohort of 22 affected individuals, thus expanding knowledge of this form of genetic thrombocytopenia.…”