Current gene therapyPub Date : 2026-01-08DOI: 10.2174/0115665232412079251105074524
Ting Zhang, Li He, Yidong Zhu
{"title":"Identification and Experimental Validation of NOP10 as a Biomarker for Diffuse Large B-Cell Lymphoma.","authors":"Ting Zhang, Li He, Yidong Zhu","doi":"10.2174/0115665232412079251105074524","DOIUrl":"https://doi.org/10.2174/0115665232412079251105074524","url":null,"abstract":"<p><strong>Introduction: </strong>Diffuse large B-cell lymphoma (DLBCL) is the most common non- Hodgkin lymphoma. Despite its high prevalence, treatment options remain limited, and molecular mechanisms underlying its pathogenesis remain poorly understood. This study aimed to identify potential biomarkers for DLBCL by integrating microarray analysis, Mendelian randomization (MR), and experimental validation.</p><p><strong>Materials and methods: </strong>DLBCL-related microarray datasets were downloaded from the Gene Expression Omnibus database. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were performed to identify hub genes in DLBCL. Moreover, we integrated genome-wide association studies data with expression quantitative trait loci to identify genes with potential causal relationships to DLBCL. The predictive power of the identified biomarker gene was evaluated using receiver operating characteristic (ROC) curves. Functional experiments were conducted to elucidate the biological roles of this gene.</p><p><strong>Results: </strong>Differential expression analysis and WGCNA identified 119 differentially expressed genes and 156 central genes, resulting in the identification of 16 hub genes in DLBCL. MR analysis revealed 188 genes with significant causal associations with DLBCL, ultimately identifying nucleolar protein 10 (NOP10) as a key biomarker. NOP10 demonstrated strong predictive performance, with the area under the curve values consistently above 0.852 across all datasets. Experimental validation in DLBCL cell lines showed that NOP10 knockdown significantly inhibited cell proliferation, induced apoptosis, and reduced the migratory capacity.</p><p><strong>Discussion: </strong>Although recent studies have made progress in identifying biomarkers associated with lymphoma onset and progression, establishing causality remains challenging due to reverse causation and confounding factors. The integration of MR in this study addressed these limitations by inferring the causality between exposure and outcome. Our findings were experimentally validated. The combination of microarray analysis and MR in our analytical approach provides a robust framework for identifying biomarker genes in various diseases and guiding the development of future therapeutic strategies.</p><p><strong>Conclusion: </strong>Our study has identified NOP10 as a promising biomarker of DLBCL, providing potential insights into the molecular mechanisms underlying this disease. Moreover, a multi-method approach integrating microarray analysis, MR, and experimental validation has established a robust framework for advancing biomarker discovery and identifying therapeutic targets for various diseases.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Current gene therapyPub Date : 2026-01-08DOI: 10.2174/0115665232425141251028050552
Muhammed Dündar, Dilek Çam Derin, İrem Nur Menevşe, Enes Gültekin, Ahmet Koç
{"title":"Targeted TP53 and KRAS Modulation <i>Via</i> AuNP-Mediated RNA Delivery Suppresses Cancer Progression.","authors":"Muhammed Dündar, Dilek Çam Derin, İrem Nur Menevşe, Enes Gültekin, Ahmet Koç","doi":"10.2174/0115665232425141251028050552","DOIUrl":"https://doi.org/10.2174/0115665232425141251028050552","url":null,"abstract":"<p><strong>Background: </strong>Small RNAs play a pivotal role in gene regulation, mediating RNAinduced transcriptional activation and post-transcriptional gene silencing. Their high specificity and versatility make them indispensable tools for investigating gene function, elucidating disease mechanisms, and developing targeted therapeutic strategies.</p><p><strong>Methods: </strong>We developed an AuNP-based RNA delivery system to enhance stability and uptake of therapeutic RNAs targeting TP53 and KRAS pathways. AuNPs were synthesized via citrate reduction and conjugated with siRNA.923 (KRAS-targeting siRNA) and dsP53-285 (p53-stimulating saRNA). A549 and HCT116 cells were transfected with conjugates. Gene expression was analyzed by RT-qPCR and Western blotting. Functional assays, including flow cytometry for cell cycle and apoptosis, MTT and colony formation assays for proliferation, and transwell assays for migration and invasion, were conducted.</p><p><strong>Results: </strong>Individual transfection of AuNP-conjugated siRNA.923 effectively downregulated KRAS expression, whereas AuNP-dsP53-285 upregulated TP53 expression in both A549 and HCT116 cell lines. Co-transfection with AuNP-siRNA.923/dsP53-285 resulted in a significantly greater increase in TP53 mRNA and protein levels, without affecting KRAS mRNA or protein levels, in both cell lines compared with individual transfections. Functionally, the AuNP-based dual small RNA delivery system induced cell cycle arrest at the G0/G1 phase, significantly enhanced apoptosis, and markedly reduced cell proliferation, colony formation, migration, and invasion relative to individual RNA transfections.</p><p><strong>Conclusion: </strong>These findings demonstrate that AuNP-mediated co-delivery of siRNA and saRNA effectively modulates the KRAS-p53 signaling axis and enhances therapeutic potential in KRASmutant, TP53-wild-type cancers. Further studies, including in vivo investigations, are warranted to evaluate the translational feasibility and clinical relevance of this combinatorial approach.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CRISPR-Cas9: A Paradigm Shift in Gene Editing Addressing Antimicrobial Resistance.","authors":"Mahima Devi, Yashika, Shubhi Saxena, Sreyosi Guha Niyogi, Komal Kishor, Shubham Thakur","doi":"10.2174/0115665232426265251126093935","DOIUrl":"https://doi.org/10.2174/0115665232426265251126093935","url":null,"abstract":"<p><p>The development of traditional antibiotics has stalled due to an escalating antimicrobial resistance (AMR) crisis. Generating new antibiotic development paradigms is critically important. CRISPR-Cas9 gene-editing technology, originally derived from the bacteria's immune system, is now being repurposed to target and neutralize antimicrobial resistance, effectively turning the bacteria's defence mechanisms against them. In this editorial, we outline the opportunities for CRISPRCas9 technology to break the microbial resistance paradigm through specific gene disruption, plasmid targeting, phage therapy, and population-based interventions. We summarize some advances related to CRISPR-Cas9 technology, including a brief overview of the technology, its component technologies, potential applications of genetic targeting, recent research related to the technology, near-future developments, and challenges. As we face an era that has been termed the \"postantibiotics\" era, CRISPR-Cas9 technology not only represents exciting technology, but also a necessary transitional change for antimicrobial products. This editorial explores recent innovations and data highlighting CRISPR-Cas9's role in addressing AMR, and the scientific, regulatory, and ethical pathways to realizing its full potential in clinical settings.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145932609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Current gene therapyPub Date : 2026-01-06DOI: 10.2174/0115665232388176251114042846
Navneet Sharma, Akash Bhati, Kamal Shah, Hitesh Kumar Dewangan
{"title":"Recent Advances on RNA-Based Molecular Therapies for Tumour Cell Targeting.","authors":"Navneet Sharma, Akash Bhati, Kamal Shah, Hitesh Kumar Dewangan","doi":"10.2174/0115665232388176251114042846","DOIUrl":"https://doi.org/10.2174/0115665232388176251114042846","url":null,"abstract":"<p><p>Anticancer drug therapy primarily focuses on exploiting genetic alterations that already exist in tumour cells. This understanding can help to utilize the conventional therapeutics with much better results. The identification of genes whose loss of function alters the tumor growth, enhances the cytotoxic characterises or leads to enhancement in the apoptotic nature of tumor cells can be done by the use of Loss-of-function genetic screens. In this review, we summarise RNAbased therapies, including mechanisms of action, clinical applications, and advancements with nanoparticles and artificial intelligence for tumor targeting in cancer. Many techniques are being explored for the promotion of RNA tracking of intracellular activities and production of metabolic stability. The emerging role of RNA in diagnosis and treatment has been a topic of discussion in the field of medical sciences. Different types of RNAs, such as small interfering RNA (siRNA), microRNA (miRNA), etc and Exosomes RNA delivery are being used for employment as the delivery system, which are considered as the therapeutic targeting system. 56 mRNA drugs have been in the pipeline for entering the clinical pipeline and nearly 108 oligonucleotide drugs are entering the clinical pipeline worldwide, including ASOs, siRNAs, aptamers and miRNAs. These different types, although they assist each other in their proper working and still function in very different ways. Most of these are under investigation, while some have been approved for clinical use. RNA-based therapies hold great potential for cancer treatment due to their specificity and adaptability. Continued research into improving delivery methods, reducing side effects, and exploring new RNA targets will be crucial in advancing these therapies to clinical practice.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145932566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Targeting Undruggable Proteins: The siRNA Revolution Beyond Small Molecules - Advances, Challenges, and Future Prospects in Therapeutic Innovation.","authors":"Sk Ashif Jan, Abhijit Debnath, Rajesh Kumar Singh, Pankaj Kumar Tyagi, Sachin Singh, Anil Kumar Singh","doi":"10.2174/0115665232357160250123113148","DOIUrl":"10.2174/0115665232357160250123113148","url":null,"abstract":"<p><p>The field of drug discovery has long been challenged by the existence of \"undruggable\" proteins - targets that have resisted traditional small molecule approaches due to their structural or functional characteristics. This review explores the revolutionary potential of small interfering RNA (siRNA) technology in addressing these elusive targets, marking a paradigm shift in therapeutic development. We discuss the historical development of siRNA technology and its unique mechanism of action, which allows for the silencing of virtually any gene, including those coding for proteins previously deemed undruggable. The review provides a comprehensive analysis of the challenges in targeting undruggable proteins and how siRNA approaches are overcoming these obstacles. We examine several case studies of undruggable targets being successfully addressed by siRNA, including oncogenic proteins like KRAS and c-Myc, transcription factors such as NF-κB and STAT3, and proteins involved in complex protein-protein interactions. The article delves into the latest advances in siRNA design, delivery systems, and targeting strategies, highlighting innovations that enhance specificity and reduce off-target effects. We also discuss the challenges facing siRNA therapeutics, including delivery obstacles, potential immune responses, and regulatory considerations. The review concludes with an exploration of future directions, including combination therapies, personalized medicine approaches, and emerging technologies that complement siRNA strategies. By providing a thorough examination of the advances, challenges, and prospects of using siRNA to target undruggable proteins, this review underscores the transformative potential of this technology in expanding the landscape of therapeutic targets and ushering in a new era of precision medicine.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"116-135"},"PeriodicalIF":3.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Gene Therapy and Gene Editing: Current Trends and Future Prospects of Molecular Medicine.","authors":"Aniruddha Sen, Vijay Singh, Shailendra Dwivedi, Ruchika Agrawal, Akash Bansal, Shashank Shekhar, Sudhir Shyam Kushwaha","doi":"10.2174/0115665232347734250211074241","DOIUrl":"10.2174/0115665232347734250211074241","url":null,"abstract":"<p><p>Gene therapy and genome editing have emerged as transformative approaches in the management of a diverse range of genetic and acquired diseases. This evaluation offers a thorough examination of the present state and prospects of these innovative technologies. Gene therapy is a prospective approach to the treatment and prevention of a variety of conditions, including complex cancers and inherited genetic disorders, which entail the introduction, removal, or modification of genetic material within a patient's cells. Genome editing, particularly through techniques such as CRISPR-Cas9, enables targeted corrections of genetic defects and opens new possibilities for personalized medicine by allowing for precise modifications at the DNA level. The review addresses the ethical implications, clinical applications, and significant advancements of these technologies. This article endeavors to underscore the substantial influence of gene therapy and genome editing on contemporary medicine by assessing the most recent research and clinical trials, thereby emphasizing their potential to revolutionize disease treatment and management.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"53-66"},"PeriodicalIF":3.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Current gene therapyPub Date : 2026-01-01DOI: 10.2174/0115665232353538250318075057
Saleem Ahmad, Hanif Khan, Njoka Irene Muthoni, Mohammed Alissa, Awaji Y Safhi, Fahad Y Sabei, Osama Abdulaziz, Khadijah Hassan Khan, Essam H Ibrahim, Safir Ullah Khan
{"title":"Riding the Wave of Progress: Examining the Current Landscape and Future Potential of MicroRNAs in Cancer Gene Therapy.","authors":"Saleem Ahmad, Hanif Khan, Njoka Irene Muthoni, Mohammed Alissa, Awaji Y Safhi, Fahad Y Sabei, Osama Abdulaziz, Khadijah Hassan Khan, Essam H Ibrahim, Safir Ullah Khan","doi":"10.2174/0115665232353538250318075057","DOIUrl":"10.2174/0115665232353538250318075057","url":null,"abstract":"<p><p>MicroRNAs, commonly referred to as miRNAs, exert a significant impact on cellular processes by coordinating post-transcriptional gene regulation. These non-coding RNAs, which are only 22 nucleotides long, form a part of the RNA-induced silencing complex (RISC) and play a crucial role in regulating gene expression. Their complex participation in cell proliferation, differentiation, and death highlights their crucial role in maintaining cellular balance. MicroRNAs have become significant contributors in the complex field of cancer biology, operating beyond the usual tasks of cells. Their dysregulation is closely intertwined with cancer initiation and development. miRNAs act as cellular regulators and regulate complex processes of gene expression. Disruption of this regulation can result in tumor development. This review article explores the intricate process of miRNA biosynthesis and its mechanisms, providing insights into its complex interactions with cancer. It also discusses the exciting field of miRNA-based cancer treatment. Exploring the therapeutic possibilities of these small RNA molecules presents opportunities for precision medicine, introducing a new age where miRNAs can be utilized to create targeted therapeutic interventions that mainly address the abnormal genetic characteristics that cause tumor formation. miRNAs provide a harmonious balance between understanding their biology and utilizing their therapeutic potential in cancer treatment. However, they also serve as conductors and possible therapeutic instruments in the symphony of molecular biology for gene therapy.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"67-84"},"PeriodicalIF":3.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Next-Generation Whole-Exome Pattern: Advanced Methods and Clinical Significance.","authors":"Sumel Ashique, Anas Islam, Navjot Kaur Sandhu, Bhavinee Sharma, Rashmi Pathak, Himanshu Sharma","doi":"10.2174/0115665232356780250331181436","DOIUrl":"10.2174/0115665232356780250331181436","url":null,"abstract":"<p><p>NGS (Next-generation sequencing) has emerged as the primary approach for gene finding in uncommon hereditary disorders. Targeted gene panels, whole genome sequencing (WGS), and whole exome sequencing (WES) are uses of next-generation sequencing and other related technologies. It is possible to explain personal or individual genome sequencing using NGS technology, as well as to detect disease-causing mutations using NGS findings. NGS, deep sequencing or massively parallel are similar words that describe a method of DNA sequencing leading to revolutionary change in genomic research. Due to its cost-effectiveness, Whole-Exome sequencing (WES) using Next-Generation Sequencing (NGS) is becoming increasingly popular in the field of human genetics. As a diagnostic tool, this technology can reduce the duration of the diagnostic process for several patients and has mostly made a significant contribution to the identification of new genes responsible for causing diseases. Considering the diverse range of phenotypic presentations of the diagnosis, NGS has the potential to uncover causative mutations, including de novo, new, and familial variants, related to epileptic syndromes and significantly enhance molecular diagnosis. The present study centres on the potential applications of next-generation exome sequencing in clinical diagnostics and the challenges encountered in the data processing of such data.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"136-151"},"PeriodicalIF":3.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Current gene therapyPub Date : 2026-01-01DOI: 10.2174/0115665232376648250312050239
Zuber Khan, Mumtaz, Sumedha Gupta, Sidharth Mehan, Tarun Sharma, Manjeet Kumar, Pankaj Kumar Maurya, Arun Kumar Sharma, Ghanshyam Das Gupta, Acharan S Narula
{"title":"CRISPR-Cas9: Transforming Functional Genomics, Precision Medicine, and Drug Development - Opportunities, Challenges, and Future Directions.","authors":"Zuber Khan, Mumtaz, Sumedha Gupta, Sidharth Mehan, Tarun Sharma, Manjeet Kumar, Pankaj Kumar Maurya, Arun Kumar Sharma, Ghanshyam Das Gupta, Acharan S Narula","doi":"10.2174/0115665232376648250312050239","DOIUrl":"10.2174/0115665232376648250312050239","url":null,"abstract":"<p><p>CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats) is a groundbreaking gene-editing technology that enables scientists to make precise changes to the DNA of living organisms. It was first discovered in Escherichia coli and emerged as a breakthrough tool in molecular biology. This technique is essential because of its adaptability, affordability, and ease of use. It uses the adaptive immune response of bacteria and archaea to repel viral invasions. It significantly influences drug discovery, functional genomics, disease models, and pharmaceutical research. CRISPR-Cas9 is a better and more accurate way to change genes than other methods, such as zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs). This technology promotes the generation of double-strand breaks in DNA, allowing for precise genetic alterations required for therapeutic target identification and confirmation. Functional genomics enables high-throughput screening (HTS) to identify gene functions, disease causes, and therapeutic targets. CRISPR-Cas9 increases drug development by enabling Cas9 to create novel antimicrobial drugs and cancer therapies. It has also helped to generate disease models, advance our understanding of neurodegenerative and other diseases, test a variety of chemicals, and facilitate precise genetic changes. Despite its promise, ethical considerations and the possibility of off-target effects require careful evaluation to ensure its safe and effective clinical application. This study investigates the current and future possibilities of CRISPR-Cas9 in drug development, focusing on its transformational influence and addressing the challenges and limitations of its therapeutic application.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"160-172"},"PeriodicalIF":3.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Current gene therapyPub Date : 2026-01-01DOI: 10.2174/0115665232415806250922094852
Ali Ors, Muhammed Burak Bereketoglu, Asli Boz, Gamze Akkus
{"title":"5-Alpha Reductase Deficiency - An Uncommon Disorder of Sexual Development: A Case Study of Four Turkish Patients within a Family.","authors":"Ali Ors, Muhammed Burak Bereketoglu, Asli Boz, Gamze Akkus","doi":"10.2174/0115665232415806250922094852","DOIUrl":"10.2174/0115665232415806250922094852","url":null,"abstract":"<p><strong>Introduction: </strong>5-alpha reductase deficiency is an inherited autosomal recessive disorder that can present with severe masculinization defects and ambiguous genitalia. Up to more than 100 mutations have been reported, but phenotype and genotype associations have not been directly evidenced. Testosterone-to-dihydrotestosterone (T/DHT) ratio is a clinically diagnostic test, and the cut-off value is expected to be higher than 10.</p><p><strong>Case presentation: </strong>This brief report of 4 patients with SRD5A2 deficiency in the same family has focused on the clinical and biochemical features of patients with the same mutation. A 14-year-old patient with c193G>C, p. Ala65Pro in SRD5A2 gene had primary amenorrhea and bilateral palpable mass in the inguinal canal. After a detailed physical examination and karyotype analysis, the patient was diagnosed with SRD5A2 deficiency with a 46, XY karyotype. In addition, the other affected siblings had the same clinical phenotype and low masculinization score. T/DHT ratio of all siblings was 14.5, 2.1, 3.7, and 19.2, respectively. Although all of them had the same genetic mutations with a homozygous pattern (c193G>C, p. Ala65Pro), a different T/DHT ratio was observed in our study.</p><p><strong>Conclusion: </strong>The definitive diagnosis of SRD5A2 deficiency requires molecular testing, but it is currently not available in some centers. Therefore, clinical phenotype and biochemical screening, especially the T/DHT ratio, should be used for evaluating this hereditary syndrome. However, we must consider that the diagnostic sensitivity of the stimulated T/DHT ratio can be affected by various factors, such as age, ethnicity, or the presence of residual enzyme activity.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"1-4"},"PeriodicalIF":3.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}