Global Medical Genetics最新文献

{"title":"The Evaluation of Prognostic Value and Immune Characteristics of Ferroptosis-Related Genes in Lung Squamous Cell Carcinoma.","authors":"Jialin Su, Shuhua Tan, Houwu Gong, Yongzhong Luo, Tianli Cheng, Hua Yang, Xiaoping Wen, Zhou Jiang, Yuning Li, Lemeng Zhang","doi":"10.1055/s-0043-1776386","DOIUrl":"10.1055/s-0043-1776386","url":null,"abstract":"<p><p><b>Background</b>  The purpose of our study was to construct a prognostic model based on ferroptosis-related gene signature to improve the prognosis prediction of lung squamous carcinoma (LUSC). <b>Methods</b>  The mRNA expression profiles and clinical data of LUSC patients were downloaded. LUSC-related essential differentially expressed genes were integrated for further analysis. Prognostic gene signatures were identified through random forest regression and univariate Cox regression analyses for constructing a prognostic model. Finally, in a preliminary experiment, we used the reverse transcription-quantitative polymerase chain reaction assay to verify the relationship between the expression of three prognostic gene features and ferroptosis. <b>Results</b>  Fifty-six ferroptosis-related essential genes were identified by using integrated analysis. Among these, three prognostic gene signatures (HELLS, POLR2H, and POLE2) were identified, which were positively affected by LUSC prognosis but negatively affected by immune cell infiltration. Significant overexpression of immune checkpoint genes occurred in the high-risk group. In preliminary experiments, we confirmed that the occurrence of ferroptosis can reduce three prognostic gene signature expression. <b>Conclusions</b>  The three ferroptosis-related genes could predict the LUSC prognostic risk of antitumor immunity.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"10 4","pages":"285-300"},"PeriodicalIF":1.2,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10615648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71427708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Possible Role of Mitochondrial Transfer RNA Gene 5816 A > G Genetic Polymorphism (m.5816A > G) in a 3-Year-Old Child with Dystonia: Report of a Case.","authors":"Sumei Wang,&nbsp;Minglu Liang,&nbsp;Jiehui Ma,&nbsp;Sheng Huang,&nbsp;Lili Fan,&nbsp;Feng Zhu,&nbsp;Dan Sun","doi":"10.1055/s-0043-1774708","DOIUrl":"10.1055/s-0043-1774708","url":null,"abstract":"<p><p><b>Background</b>  Mutations in the mitochondrial transfer RNA (mt-tRNA) gene are a hotspot for mitochondrial DNA (mtDNA) mutations and are most common in mitochondrial diseases. <b>Methods</b>  We identified the mt-tRNA gene 5816 A > G (m.5816 A > G) mutation in a 3-year-old child with dystonia who died. We performed clinical evaluation, genetic analysis, and biochemical investigation with mitochondrial function testing. <b>Results</b>  Our patient was found to have dystonia with hyperlactatemia. Electroencephalogram findings were abnormal in children with numerous multifocal spikes, multispike, spikes and slow waves, slow waves and low amplitude fast waves, more pronounced in the occipital region bilaterally, and occurring continuously during sleep. One year later, the preexisting patient had seizures lasting 1 to 2 hours and subsequently died. mtDNA sequencing revealed that the proband, her mother, and her grandmother all carried the m.5816A > G mutation. Oxygen consumption rate (OCR) assays revealed that the proband's basal resting OCR, adenosine triphosphate production, proton leak, maximal respiration, and spare capacity OCR were all significantly lower compared with healthy children of the same age. <b>Conclusion</b>  The present case demonstrates a childhood dystonia caused by a mt-tRNA gene 5816 A > G mutation, which has never been reported before. Our findings provide valuable new insights into the pathogenic mechanism and function of the m.5816A > G mutation.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"10 3","pages":"263-270"},"PeriodicalIF":1.7,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10533220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41104641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>ADAR</i> Expression and Single Nucleotide Variants in Multiple Sclerosis Patients Affect the Response to Interferon Beta Therapy.","authors":"Fatemeh Fakhr,&nbsp;Vahid Shaygannejad,&nbsp;Mehdi Khorrami,&nbsp;Leila Saberi,&nbsp;Omid Mirmosayyeb,&nbsp;Erfan Sadeghi,&nbsp;Majid Kheirollahi","doi":"10.1055/s-0043-1771001","DOIUrl":"https://doi.org/10.1055/s-0043-1771001","url":null,"abstract":"<p><p>Interferon (IFN)-β is the first-line disease management choice in multiple sclerosis (MS) with profound effects; however, in up to 50% of patients, clinical response does not occur. Ascertaining the responding state, need a long-term clinical follow-up, and this may lead to delay in use of other effective medications. IFN-induced cascade and its regulation is considered to play a major role in MS. Adenosine deaminase, RNA-specific (ADAR) dysregulation is important to IFN signaling pathway as an activity suppressor. Hence, we investigated the expression of <i>ADAR</i> and its single nucleotide variants of rs2229857 association with response to IFN-β in relapsing-remitting MS patients. mRNA levels and genotyping of rs2229857 in 167 MS patients were investigated via SYBR Green real-time (RT)-quantitative polymerase chain reaction and high-resolution melting RT PCR, respectively. The allele-A in rs2229857 and higher expression of <i>ADAR</i> were associated with poor response to IFN-β. Two response groups were significantly different in terms of annualized relapse rate, first symptoms, first extended disability status scale (EDSS), current EDSS, and the MS severity score. According to this study's findings, assessment of transcript levels and also variants in ADAR may be useful in identifying patients' response to IFN-β before starting treatment. Further investigations are needed to determine the potency of ADAR to be a predictive biomarker in drug responsiveness.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"10 3","pages":"164-171"},"PeriodicalIF":1.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10370467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9941492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Diagnosis of Hemophilia A and Pathogenesis of Novel F8 Variants in Shanxi, China.","authors":"Xialin Zhang,&nbsp;Kun Chen,&nbsp;Sicheng Bian,&nbsp;Gang Wang,&nbsp;Xiuyu Qin,&nbsp;Ruijuan Zhang,&nbsp;Linhua Yang","doi":"10.1055/s-0043-1774322","DOIUrl":"https://doi.org/10.1055/s-0043-1774322","url":null,"abstract":"<p><p>The aim of this study was to perform a molecular diagnosis of hemophilia A (HA) among patients in the Shanxi Province of China. Fifty-two HA patients were tested, including IVS22 (31 samples), IVS1 (3 samples), missense (11 samples), nonsense (3 samples), and 4 cases of frameshift (2 cases of deletion, 1 case of insertion, 1 case of single-base duplication). With the exception of the single-base G duplication variant (p.Ile1213Asnfs*28), this was the hotspot variant reported by research groups at an early stage. The remaining variants were found, for the first time, in the region. The missense variants p.Cys172Ser, p.Tyr404Ser, p.Asp1903Gly, and p.Ser2284Asn, the deletion variant p.Leu2249fs*9, and the insertion variant p.Pro2319fs*97 were novel variants. The application of next-generation sequencing (NGS) molecular diagnosis enriched the variant spectrum of HA, which is greatly significant for individualized genetic counseling, clinical diagnosis, and treatment. NGS and a variety of bioinformatics prediction methods can further analyze the impact of genetic variation on protein structure or function and lay the foundation to reveal the molecular pathogenic mechanism of novel variants.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"10 3","pages":"247-262"},"PeriodicalIF":1.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10499503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10264607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shared Genes and Molecular Mechanisms between Nonalcoholic Fatty Liver Disease and Hepatocellular Carcinoma Established by WGCNA Analysis.","authors":"Juan He,&nbsp;Xin Zhang,&nbsp;Xi Chen,&nbsp;Zongyao Xu,&nbsp;Xiaoqi Chen,&nbsp;Jiangyan Xu","doi":"10.1055/s-0043-1768957","DOIUrl":"https://doi.org/10.1055/s-0043-1768957","url":null,"abstract":"<p><p><b>Background</b>  Hepatocellular carcinoma (HCC) is one of the leading causes of death from cancer worldwide. The histopathological features, risk factors, and prognosis of HCC caused by nonalcoholic fatty liver disease (NAFLD) appear to be significantly different from those of HCC caused by other etiologies of liver disease. <b>Objective</b>  This article explores the shared gene and molecular mechanism between NAFLD and HCC through bioinformatics technologies such as weighted gene co-expression network analysis (WGCNA), so as to provide a reference for comprehensive understanding and treatment of HCC caused by NAFLD. <b>Methods</b>  NAFLD complementary deoxyribonucleic acid microarrays (GSE185051) from the Gene Expression Omnibus database and HCC ribonucleic acid (RNA)-sequencing data (RNA-seq data) from The Cancer Genome Atlas database were used to analyze the differentially expressed genes (DEGs) between NAFLD and HCC. Then, the clinical traits and DEGs in the two disease data sets were analyzed by WGCNA to obtain W-DEGs, and cross-W-DEGs were obtained by their intersection. We performed subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) enrichment analyses of the cross-W-DEGs and established protein-protein interaction networks. Then, we identified the hub genes in them by Cytoscape and screened out the final candidate genes. Finally, we validated candidate genes by gene expression, survival, and immunohistochemical analyses. <b>Results</b>  The GO analysis of 79 cross-W-DEGs showed they were related mainly to RNA polymerase II (RNAP II) and its upstream transcription factors. KEGG analysis revealed that they were enriched predominantly in inflammation-related pathways (tumor necrosis factor and interleukin-17). Four candidate genes (JUNB, DUSP1, NR4A1, and FOSB) were finally screened out from the cross-W-DEGs. <b>Conclusion</b>  JUNB, DUSP1, NR4A1, and FOSB inhibit NAFLD and HCC development and progression. Thus, they can serve as potential useful biomarkers for predicting and treating NAFLD progression to HCC.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"10 3","pages":"144-158"},"PeriodicalIF":1.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10370469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9887021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VEXAS Syndrome-Review.","authors":"Yue Zhang,&nbsp;Xifeng Dong,&nbsp;Huaquan Wang","doi":"10.1055/s-0043-1770958","DOIUrl":"https://doi.org/10.1055/s-0043-1770958","url":null,"abstract":"<p><p>VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly defined refractory adult-onset autoinflammatory syndrome caused by somatic mutations in the ubiquitin-like modifier-activating enzyme 1 (UBA1) gene in hematopoietic stem and progenitor cells, resulting in a shift in UBA1 isoform expression. Thus, patients develop a spectrum of systemic inflammatory manifestations and hematologic symptoms. To date, patients respond poorly to immune suppressive drugs, except high-dose glucocorticoids, and no treatment guidelines have been established. Given the high mortality rate, VEXAS syndrome needs to be taken seriously by physicians in all specialties. This article aims to describe the key features, pathogenesis, and clinical manifestations of VEXAS syndrome to better understand the targeted treatment and improve the prognosis of VEXAS syndrome.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"10 3","pages":"133-143"},"PeriodicalIF":1.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10370470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9941491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of CD44 in Head and Neck Squamous Cell Carcinoma-An <i>In-Silico</i> Study.","authors":"Loganathan Kavitha,&nbsp;Jayaseelan Vijayashree Priyadharsini,&nbsp;Deepthi Kattula,&nbsp;Umadevi Krishna Mohan Rao,&nbsp;Rajabather Balaji Srikanth,&nbsp;Manogaran Kuzhalmozhi,&nbsp;Kannan Ranganathan","doi":"10.1055/s-0043-1772459","DOIUrl":"https://doi.org/10.1055/s-0043-1772459","url":null,"abstract":"<p><p><b>Introduction</b>  CD44, a multistructural and multifunctional transmembrane glycoprotein, is a promising cancer stem cell (CSC) marker that regulates the properties of CSCs, including self-renewal, tumor initiation, and metastasis, and confers resistance to chemotherapy and radiotherapy. The aim of the present study was to evaluate the gene and protein expression of CD44 and explore its prognostic value in head and neck squamous cell carcinoma (HNSCC). <b>Methodology</b>  The present observational study employs computational tools for analysis. The Cancer Genome Atlas Head-Neck Squamous Cell Carcinoma dataset (520 primary HNSCC and 44 normal tissues) from the University of Alabama at Birmingham Cancer platform was used to study the association of CD44 mRNA transcript levels with various clinicopathological characteristics of HNSCC including age, gender, tumor grade, tumor stage, human papillomavirus (HPV) status, p53 mutation status, and overall survival. The CD44 protein expression in HNSCC and normal tissues was ascertained using the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium Head-and-Neck cancer dataset (108 primary HNSCC and 71 normal tissues). <b>Results</b>  CD44 mRNA transcript and protein expression levels were significantly higher in HNSCC tissues than in normal tissues, and high CD44 expression was correlated with poor survival. CD44 was upregulated in Stage 1 and Grade 2 HNSCC compared with other stages and grades. Overexpression of CD44 was observed in HPV-negative and TP53-positive mutant status in HNSCC. <b>Conclusion</b>  The pleiotropic roles of CD44 in tumorigenesis urge the need to explore its differential expression in HNSCC. The study concludes that CD44 can be a potential diagnostic and prognostic biomarker for HNSCC and offer new molecular targets for CD44-targeted therapy for cancer management.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"10 3","pages":"221-228"},"PeriodicalIF":1.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10431972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10049986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lessons from Real Life Experience: Importance of In-House Sequencing and Smart Ratio-Based Real-Time PCR Outperform Multiplex Ligation-Dependent Probe Amplification in Prenatal Diagnosis for Spinal Muscular Atrophy: Bench to Bedside Diagnosis.","authors":"Gulten Tuncel,&nbsp;Burcin Sanlıdag,&nbsp;Eray Dirik,&nbsp;Tugba Baris,&nbsp;Mahmut Cerkez Ergoren,&nbsp;Sehime Gulsun Temel","doi":"10.1055/s-0043-1774307","DOIUrl":"https://doi.org/10.1055/s-0043-1774307","url":null,"abstract":"<p><p>Spinal muscular atrophy (SMA) is a rare, recessively inherited neurodegenerative disorder caused by the presence of pathogenic variants in the <i>SMN</i> gene. As it is the leading inherited cause of infant mortality, identification of <i>SMN</i> gene pathogenic variant carriers is important for diagnostic purposes with effective genetic counseling. Multiple ligation probe analysis (MLPA), a probe-based method, is considered as the gold standard for SMA carrier analysis. However, MLPA might give false-negative results in cases with variations in the probe-binding regions. Here, we present a case born to consanguineous SMA carrier parents. Prenatal diagnosis with MLPA failed to detect the compound heterozygous mutant state of the proband and she was born unfortunately with SMA phenotype. Further analysis with a real-time polymerase chain reaction kit was able to detect the compound heterozygous state of the patient and was confirmed with targeted next-generation sequencing technology.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"10 3","pages":"240-246"},"PeriodicalIF":1.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10471427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10506056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Review: Advances in the Pathogenesis and Treatment of Immune Thrombocytopenia Associated with Viral Hepatitis.","authors":"Yanmei Xu,&nbsp;Yunfei Chen,&nbsp;Lei Zhang","doi":"10.1055/s-0043-1772771","DOIUrl":"https://doi.org/10.1055/s-0043-1772771","url":null,"abstract":"<p><p>Hepatitis B virus and hepatitis C virus are the hepatitis subtypes that most commonly induce immune thrombocytopenia (ITP). Although the pathogenesis of viral hepatitis-associated ITP remains unclear, it may involve antibody cross-reactivity due to molecular mimicry, the formation of virus-platelet immune complexes, and T cell-mediated suppression of bone marrow hematopoiesis. Moreover, there is significant correlation between platelet count and the severity of viral hepatitis, the risk of progression to liver cirrhosis, and clinical prognosis. However, treatment of viral hepatitis-associated ITP is hindered by some antiviral drugs. In this review, we summarize research progress to date on the pathogenesis and treatment of viral hepatitis-related ITP, hoping to provide a reference for clinical diagnosis and treatment.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"10 3","pages":"229-233"},"PeriodicalIF":1.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10449570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10463598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strokelike Episodes in <i>PMM-2</i> Carriers Differ from Those in Mitochondrial Disorders.","authors":"Josef Finsterer","doi":"10.1055/s-0043-1771183","DOIUrl":"https://doi.org/10.1055/s-0043-1771183","url":null,"abstract":"We read with interest the article by Sreedevi et al who reported the case of a 12-year-old girl with a congenital disorder of glycosylation (CDG) due to the variant c.710C > T in the phosphomannomutase-2 ( PMM2 ) gene. 1 The patient manifested phenotypically with developmental delay, cog-nitive impairment, generalized hypotonia","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"10 3","pages":"188-189"},"PeriodicalIF":1.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10348842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10184756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}