Background
Isolated sulfite oxidase deficiency (ISOD) is a life‐threatening rare autosomal recessive disorder caused by pathogenic variants in SUOX (OMIM 606887) gene. The aim of our study was to establish a comprehensive genetic diagnosis strategy for the pathogenicity analysis of the SUOX gene within a limited time and to lay the foundation for precise genetic counseling, prenatal diagnosis, and preimplantation genetic diagnosis.
Methods
Two offspring from one set of parents were studied. Next‐generation sequencing (NGS) was used to screen for disease‐causing gene variants in a family with ISOD. Then, Sanger sequencing was performed to verify the presence of candidate variants. Sulfite, homocysteine and uric acid levels were detected in the patients. According to the ACMG/AMP guidelines, the pathogenicity level of novel variants was annotated.
Results
The nonsense pathogenic variant (c.1200C > G (p.Y400*)) and a duplication (c.1549_1574dup (p.I525 Mfs*102)) were found in the SUOX gene in the proband. The nonsense mutation (c.1200C > G (p.Y400*), pathogenic, isolated sulfite oxidase deficiency, autosomal recessive) has been reported as pathogenic and the duplication (c.1549_1574dup (p.I525 Mfs*102), pathogenic, isolated sulfite oxidase deficiency, autosomal recessive) was novel, which was classified as pathogenic according to the ACMG/AMP Standards and Guidelines.
Conclusion
We established the pathogenicity assessment in ISOD patients based on ACMG/AMP Standards and Guidelines and this is the first ISOD patient reported in mainland China. We also discovered that ISOD is caused by SUOX gene duplication mutation, which enriches the spectrum of SUOX pathogenic variants.
We first established the PND procedure with pathogenicity assessment in FXIIID patients. The F13A gene mutations' spectrum of the Chinese Han population was enriched.
The present study aimed to examine the effects of nicotinamide (NAM) on cervical cancer-associated fibroblasts (CAF) for its in vitro efficacy, gross inhibition, and mechanism of inhibition. Methods: The fibroblasts were treated with pre-specified concentrations of NAM followed by measurement of the cell proliferation using CCK-8 assay. The production of reactive oxygen species (ROS) was measured by 2ʹ,7ʹ-Dichlorofluorescin diacetate. We further investigated the apoptosis by flow cytometry using Annexin-V. We employed JC-1 assay to detect changes in the potential of the mitochondrial membrane. We further determined the expression of apoptotic genes was measured using qRT-PCR. And lastly, cell cycle experiments were conducted to determine the influence of NAM on arresting the growth of CAF in a cell cycle. Results: Our study showed that NAM was able to reduce fibroblasts viability. We specifically observed a significantly increased intracellular ROS with resultant exhaustion of cellular antioxidant defense machinery, including reduced glutathione (GSH). We further observed the involvement of mitochondrial pathway in the NAM induced apoptosis of fibroblasts. Conclusion: Our study supports the therapeutic potential of NAM for the treatment of cervical cancer and necessitates a further investigation of the reported findings.
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