Human Gene最新文献

{"title":"Multiple sclerosis: The role of miRNAs and their implications in cellular pathways","authors":"Doha El-Sayed Ellakwa ,&nbsp;Arwa Amer ,&nbsp;Aya Ibrahim ,&nbsp;Rana Aboeleneen ,&nbsp;Al-Hassan Soliman Wadan ,&nbsp;Takwa E. Ellakwa","doi":"10.1016/j.humgen.2026.201562","DOIUrl":"10.1016/j.humgen.2026.201562","url":null,"abstract":"<div><div>Multiple sclerosis [MS] is a chronic autoimmune disorder characterized by inflammatory damage to the central nervous system, leading to progressive myelin degradation and neurological impairment. MicroRNAs [miRNAs] have been identified as key regulators in MS pathogenesis, with their expression being influenced by environmental, genetic, and immunological factors. Specific miRNAs, including miR-155, miR-150, and the miR-15a/16–1 cluster, are linked to dysregulated immune responses and disease progression. Moreover, the stability of miRNAs in bodily fluids positions them as potential non-invasive biomarkers for MS diagnosis. However, despite these advancements, MS remains a complex condition that is challenging to diagnose and treat effectively. The heterogeneity of the disease and the intricate regulatory mechanisms governing miRNA expression present significant barriers to the development of targeted therapies and reliable biomarkers. This review examines the diverse functions of miRNAs in MS, emphasizing their dual role as biomarkers and therapeutic targets. It discusses the distinct miRNA expression profiles identified in the serum and cerebrospinal fluid of MS patients, which may contribute to improved diagnostic precision. Additionally, advancements in miRNA delivery and modulation technologies are explored as promising therapeutic strategies to restore immune balance and reduce neuroinflammation. By harnessing these insights, researchers may refine diagnostic tools and develop targeted treatments, ultimately enhancing clinical outcomes for MS patients. This review highlights the necessity for further investigation into miRNA-based approaches, advocating for continued research to fully realize their potential in advancing MS diagnosis and therapeutic strategies.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"48 ","pages":"Article 201562"},"PeriodicalIF":0.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147797983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic surveillance with next-generation sequencing in neonatal sepsis: Emerging tools for precision medicine","authors":"Vijay Laxmi,&nbsp;Sheetal Verma,&nbsp;Vimala Venkatesh,&nbsp;Mohit,&nbsp;Jayhind Maury,&nbsp;Ankita Yadav","doi":"10.1016/j.humgen.2026.201557","DOIUrl":"10.1016/j.humgen.2026.201557","url":null,"abstract":"<div><div>Neonatal sepsis remains a leading cause of morbidity and mortality worldwide, particularly in low- and middle-income countries, despite advances in neonatal intensive care. Traditional diagnostic methods for neonatal sepsis, including blood cultures, are limited by suboptimal sensitivity and prolonged turnaround times, which can delay targeted antimicrobial therapy and contribute to extended exposure to broad-spectrum antibiotics. Next-generation sequencing (NGS) is a culture-independent diagnostic approach that may broaden pathogen detection; however, its sensitivity, turnaround time, and established clinical utility in neonatal blood specimens are still being evaluated. This high-throughput technology has the potential to improve diagnostic capabilities in neonatal sepsis by detecting both common and rare organisms. This genomic approach may support precision treatment strategies by identifying antimicrobial resistance genes and informing antibiotic selection based on resistance profiling. Additionally, NGS offers opportunities to explore host-response signatures that may assist in risk stratification. However, these applications remain investigational, and their role in predicting neonatal sepsis risk and clinical outcomes through genomic profiling, including the analysis of gene interactions and antimicrobial resistance (AMR) associated mutations requires further validation. Besides these advantages, some limitations still exist, such as high cost, the need for trained personnel, resource constraints and challenges with accurate clinical interpretations. Regulatory guidelines and clinical integration frameworks are still evolving, and NGS is currently regarded as a complementary rather than routine diagnostic tool, as recommendations for its standardized use in neonatal sepsis remain under development. This article discusses and summarizes clinical evidence and highlights implementation barriers, offering a novel perspective on the upcoming roadmap for NGS integration in neonatal sepsis. It highlights the need for future multi-centric genomic surveillance, standardization of interpretation tools, genomic antimicrobial stewardship may enhance its role in advancing personalized and evidence-based neonatal care.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"48 ","pages":"Article 201557"},"PeriodicalIF":0.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147797984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The OIP5-AS1/miR-199a-3p/FN1 ceRNA axis modulates extracellular matrix remodelling and invasive signaling in oral squamous cell carcinoma","authors":"K.P. Ameya,&nbsp;P.P. Ashikha Shirin Usman,&nbsp;Durairaj Sekar","doi":"10.1016/j.humgen.2026.201563","DOIUrl":"10.1016/j.humgen.2026.201563","url":null,"abstract":"<div><h3>Purpose</h3><div>Oral squamous cell carcinoma (OSCC) remains a highly aggressive malignancy with poor clinical outcomes due to late diagnosis and the lack of robust molecular biomarkers. Emerging evidence suggests that competing endogenous RNA (ceRNA) networks involving non-coding RNAs play critical roles in cancer progression; however, OSCC-specific regulatory axes remain incompletely understood. This study aimed to identify and characterize a novel ceRNA regulatory network involving OIP5-AS1, miR-199a-3p, and FN1, and to elucidate its functional and clinical relevance in OSCC.</div></div><div><h3>Principal results</h3><div>Integrated in silico analysis of TCGA datasets revealed significant downregulation of miR-199a-3p and concurrent upregulation of lncRNA OIP5-AS1 and FN1 in OSCC tissues. Bioinformatic predictions and network analyses supported a ceRNA mechanism whereby OIP5-AS1 acts as a molecular sponge for miR-199a-3p, leading to derepression of FN1. Elevated expression of OIP5-AS1 and FN1, together with reduced miR-199a-3p levels, correlated with advanced tumor stage, enhanced invasive potential, and poor prognosis. Functional enrichment and pathway analyses implicated this axis in extracellular matrix remodelling, oncogenic signaling pathways, and tumor microenvironment modulation. These findings were experimentally validated through quantitative real-time PCR in OSCC clinical tissue samples and in OSCC cell lines with differing invasive capacities.</div></div><div><h3>Major conclusions</h3><div>The present study identifies the OIP5-AS1/miR-199a-3p/FN1 axis as a critical ceRNA-mediated regulatory network driving OSCC progression. Its consistent association with tumor aggressiveness and clinical severity highlights its potential utility as a diagnostic and prognostic biomarker, as well as a promising target for future therapeutic intervention in OSCC.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"48 ","pages":"Article 201563"},"PeriodicalIF":0.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147850136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence enhanced CRISPR based epigenomic editing: A brighter future in precision medicine","authors":"Himani Dange ,&nbsp;Chandrakant Bonde ,&nbsp;Smita Bonde ,&nbsp;Kalpana Pandya ,&nbsp;Devendra Kumar ,&nbsp;Jineetkumar Gawad","doi":"10.1016/j.humgen.2026.201565","DOIUrl":"10.1016/j.humgen.2026.201565","url":null,"abstract":"<div><div>This review discusses the convergence of clustered regularly interspaced short palindromic repeats (CRISPR)-based epigenomic editing and artificial intelligence (AI) and their synergistic potential in gene regulation and disease therapy. CRISPR-based epigenomic editing, focused on deactivated Cas9, allows for targeted epigenetic marker modifications like DNA methylation and histone modifications without changing the DNA sequence. This method has the potential to reveal and cure multifaceted diseases such as cancer and neurological diseases by reversing erroneous gene function. The combination of AI, specifically machine learning and deep learning, improves the accuracy and efficiency of CRISPR-based systems. AI models enhance guide RNA design, forecast off-targeting effects, and incorporate multi-omics data to gain an in-depth understanding of gene regulation. These innovations enable early detection of disease, customized therapies, and prevention by finding epigenetic biomarkers and risk factors. The CRISPR-AI combination also opens doors for real-time treatment response monitoring and adaptive therapies with the potential for dynamic adaptation to patient-specific epigenetic information. Nevertheless, ethical concerns and technical hurdles like data complexity and model generalizability need to be overcome to utilize these opportunities responsibly. The convergence of CRISPR and AI technologies holds transformative promise for precision medicine, from the early detection of disease to personalized interventions.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"48 ","pages":"Article 201565"},"PeriodicalIF":0.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147850134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Concurrence of Prader-Willi syndrome and Fabry disease: First case report and family-based analysis of a unique dual molecular diagnosis","authors":"Ye-Ting Hu ,&nbsp;Yong-Xue Lyu ,&nbsp;Yi Gao","doi":"10.1016/j.humgen.2026.201564","DOIUrl":"10.1016/j.humgen.2026.201564","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to investigate the clinical phenotype and familial genetic characteristics of a rare case with concurrent 15q11.2–q13.1 deletion and a GLA gene variant, providing a reference for early diagnosis and family management of such complex genetic disorders.</div></div><div><h3>Methods</h3><div>A retrospective analysis was performed on a female infant who presented at 1 month and 25 days of age with feeding difficulties and hypotonia. Whole-exome sequencing (WES) and methylation-specific multiplex ligation-dependent probe amplification were conducted for genetic validation. Family members were screened for the GLA variant and assessed for α-galactosidase A (α-Gal A) activity.</div></div><div><h3>Results</h3><div>The patient had feeding difficulties, hypotonia, growth delay, and hip dysplasia. WES revealed a 5.48 Mb heterozygous deletion in 15q11.2–q13.1, confirmed by abnormal methylation indicating paternal origin. Concurrently, WES identified a paternally inherited GLA splicing variant (c.640-801G &gt; A), classified as pathogenic by American College of Medical Genetics and Genomics criteria. Aside from typical Prader-Willi syndrome features, the patient had no Fabry disease symptoms. The father had diarrhea, acroparesthesia, hypohidrosis, fatty liver, a renal cyst, and mild left ventricular dysfunction. The grandmother carried the same GLA variant with reduced α-Gal A activity but was asymptomatic. The patient started recombinant human growth hormone at 3 months; at 1-year follow-up, her height and weight were normal, with improved motor and feeding functions.</div></div><div><h3>Conclusions</h3><div>This first reported case of concurrent 15q11.2–q13.1 deletion and a GLA variant highlights the phenotypic impact of multiple genetic variations. Genetic testing facilitates early identification, genetic counseling, and individualized follow-up. The personalized treatment strategy and dynamic risk assessment offer insights for managing similar complex cases.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"48 ","pages":"Article 201564"},"PeriodicalIF":0.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147850133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole-exome sequencing identifies a novel variant within the ARSB gene causing mucopolysaccharidosis type VI in an Iranian patient","authors":"Elham Alimoradi ,&nbsp;Parham Nejati ,&nbsp;Sanaz Bahadori ,&nbsp;Fatemeh Molavi ,&nbsp;Soudeh Ghafouri-Fard ,&nbsp;Reza Alibakhshi","doi":"10.1016/j.humgen.2026.201561","DOIUrl":"10.1016/j.humgen.2026.201561","url":null,"abstract":"<div><h3>Background</h3><div>Mucopolysaccharidosis type VI (MPS VI) is a rare lysosomal storage disorder caused by pathogenic variants in the <em>ARSB</em> gene, encoding the enzyme arylsulfatase B.</div></div><div><h3>Methods</h3><div>We reported the clinical and molecular characterization of a novel homozygous variant in the <em>ARSB</em> gene in an Iranian patient with MPS VI. The proband's DNA underwent whole-exome sequencing (WES). Identified variants were filtered and analyzed using bioinformatics tools and databases. The pathogenic impact of the variant was assessed using <em>in silico</em> prediction tools and protein modeling.</div></div><div><h3>Results</h3><div>The patient had the classic manifestations of MPS VI, including coarse facies, skeletal dysplasia, organomegaly, and elevated urinary glycosaminoglycans. WES identified a novel homozygous missense variant, c.982G &gt; C (p.Gly328Arg), in exon 5 of the <em>ARSB</em> gene (NM_000046.5). <em>In silico</em> analyses, including HOPE, mCSM, SDM, and DUET, unanimously predicted this variant to be destabilizing and deleterious. Additionally, protein modeling indicated a significant structural alteration due to the substitution of a small, non-polar glycine with a larger, positively charged arginine. Taken together, we report a novel variant, c.982G &gt; C (p.Gly328Arg), in the <em>ARSB</em> gene, expanding the mutational spectrum of MPS VI among Iranians. This finding underscores the utility of WES in diagnosing rare metabolic disorders and facilitates accurate genetic counseling for the affected family.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"48 ","pages":"Article 201561"},"PeriodicalIF":0.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147850132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of clinical features, differential gene expression, and immune infiltration in female genital tuberculosis using RNA sequencing and bioinformatics analysis","authors":"Qi Wang ,&nbsp;Yaping Chen ,&nbsp;Yanfen Liu ,&nbsp;Bei Xie ,&nbsp;Huijuan Deng ,&nbsp;Fanrong Meng ,&nbsp;Nan Wang ,&nbsp;Defang Xiong ,&nbsp;Yuanjin Chen ,&nbsp;Zeyou Wei ,&nbsp;Pengyan Dong ,&nbsp;Bo Huang ,&nbsp;Yu Yang ,&nbsp;Xiaomin Lai ,&nbsp;Zhihui Liu ,&nbsp;Hua Li ,&nbsp;Weiyun He","doi":"10.1016/j.humgen.2026.201538","DOIUrl":"10.1016/j.humgen.2026.201538","url":null,"abstract":"<div><div>Female Genital Tuberculosis (FGTB) represents a rare but severe condition that significantly impacts women’s reproductive health and overall quality of life, incurring substantial economic burdens for both patients and society. The current diagnostic and therapeutic approaches for FGTB are limited, often resulting in delayed diagnosis and less than optimal treatment outcomes. This study aimed to elucidate the clinical characteristics of FGTB while identifying differentially expressed genes (DEGs) involved in its pathogenesis and immune response. We employed RNA sequencing and bioinformatics analyses of clinical samples to thoroughly evaluate the gene expression profiles of FGTB patients in comparison to healthy controls, revealing a total of 16,194 DEGs, comprising 588 upregulated and 179 downregulated genes, indicating significant differences between the two groups. Pathway analysis suggested that alterations in the complement/coagulation cascade, MAPK signaling, HIF-1 signaling, and IL-17 signaling pathways may elucidate the immune evasion mechanisms underlying FGTB. Moreover, key regulatory genes such as MMP8, CTSG, and AHSP were identified as influential in modulating immune infiltration responses, potentially altering the immune microenvironment. Notably, MMP8–Docetaxel exhibiting favorable binding energies in molecular docking, molecular dynamics Simulation and MM/PBSA Analysis. In conclusion, our findings provide a comprehensive understanding of the clinical features, gene expression alterations, and immune landscape in FGTB, paving the way for novel insights into early diagnosis and therapeutic strategies. Future research should prioritize larger sample sizes and clinical validation to further advance the understanding and management of this debilitating condition.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"47 ","pages":"Article 201538"},"PeriodicalIF":0.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of IL-6R gene polymorphism (rs8192284) on type 2 diabetes mellitus and other metabolic disorders in the Bangladeshi population","authors":"Amirul Kabir,&nbsp;Md. Abdullah Al Mamun Khan,&nbsp;K.M. Kaderi Kibria","doi":"10.1016/j.humgen.2026.201536","DOIUrl":"10.1016/j.humgen.2026.201536","url":null,"abstract":"<div><h3>Background</h3><div>Type 2 diabetes mellitus (T2DM) is a multifactorial, polygenic metabolic disorder. This study aimed to investigate the prevalence of the Asp358Ala polymorphism in the IL-6R gene (rs8192284) in the Bangladeshi population and its association with specific metabolic syndromes.</div></div><div><h3>Method</h3><div>A total of 359 subjects (178 patients with type 2 diabetes and 181 non-diabetic controls) were enrolled from various healthcare centers in Bangladesh. Lifestyle factors and anthropometric data were gathered from study subjects using a standard questionnaire. Blood samples were collected for DNA extraction, and allele-specific PCR was performed for genotyping the SNP in the IL-6R gene. Accurate genotyping results were ensured by optimizing primer design and PCR conditions and validating them using DNA sequencing. The association between these data was analyzed using SPSS.</div></div><div><h3>Result</h3><div>IL6R polymorphisms showed no overall significant relationship with type 2 diabetes (<em>P</em> = 0.102); however, after analyzing according to the inheritance model, the dominant model was found to be significantly related to diabetes (<em>P</em> = 0.043). This suggests that the homozygous wild-type allele is more prone to diabetes, whereas the mutation appears to be associated with a reduced risk. Diabetic patients were also susceptible to pre-high and high blood pressure (<em>P</em> = 0.03). The assessment of SNP with a dominant model reveals an association between the A/A genotype and hypertension (<em>P</em> = 0.043). Analysis of variance revealed that diastolic blood pressure levels were elevated primarily in the A/A genotype (<em>P</em> = 0.019).</div></div><div><h3>Conclusion</h3><div>The study suggests that the IL6R polymorphism is associated with a reduced risk of diabetes. Additionally, the A/A genotype is responsible for hypertension, particularly diastolic blood pressure.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"47 ","pages":"Article 201536"},"PeriodicalIF":0.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of NSD1 gene expression in cancer pathogenesis: Opportunities for personalized therapeutics","authors":"Mahintaj Dara ,&nbsp;Mehdi Dianatpour ,&nbsp;Negar Azarpira ,&nbsp;Sarina Pourjafar","doi":"10.1016/j.humgen.2026.201535","DOIUrl":"10.1016/j.humgen.2026.201535","url":null,"abstract":"<div><div>The histone methyltransferase NSD1 has emerged as a context-dependent master regulator in cancer pathogenesis, presenting both unique challenges and opportunities for precision oncology. This review synthesizes evidence that NSD1 dysregulation through mutations, fusions, or epigenetic silencing disrupts H3K36 methylation landscapes, driving tumorigenesis in a tissue-specific manner. Notably, NSD1 can function as either an oncogene or a tumor suppressor, a duality that critically informs its utility as a prognostic biomarker and therapeutic target. We critically evaluate the current therapeutic landscape, moving beyond the unsuccessful pursuit of conventional catalytic inhibitors to highlight more promising strategies. These include targeted protein degradation via PROTACs, RNAi-based silencing of oncogenic fusions, and leveraging synthetic lethality by targeting downstream pathways like AKT/mTOR. Finally, we discuss the imperative for developing epigenetic biomarkers to guide patient stratification. Overcoming the challenges of NSD1 targeting holds the potential to deliver novel, effective therapies for defined cancer populations.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"47 ","pages":"Article 201535"},"PeriodicalIF":0.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In utero gene therapy: Pioneering diagnostic and therapeutic technologies","authors":"Shalmoli Seth ,&nbsp;Malini Sen ,&nbsp;Souvik Banerjee ,&nbsp;Ritamay Sau ,&nbsp;Somasree Ray","doi":"10.1016/j.humgen.2025.201527","DOIUrl":"10.1016/j.humgen.2025.201527","url":null,"abstract":"<div><div>Advancements in prenatal imaging, molecular diagnostics, and genetic screening have transformed the management of congenital diseases, enabling early identification and treatment in utero. These innovations facilitate medical interventions before clinical symptoms arise, improving outcomes and reducing disease severity. Advanced genetic testing of blood, tissue, and other biological samples, combined with techniques such as fluorescence in situ hybridization and chromosomal microarray analysis, allows precise detection and classification of monogenic, mitochondrial, chromosomal, and multifactorial disorders. Emerging in utero therapies, particularly gene therapy, leverage the fetus's unique developmental properties to provide targeted and minimally invasive treatment for structural and genetic abnormalities. However, key challenges remain, such as ensuring biocompatibility and achieving efficient intracellular transgene delivery. Progress in viral and non-viral delivery systems and advancements in gene editing technologies have shown potential in overcoming these obstacles, paving the way for clinical translation. Nanotechnology further enhances these efforts by providing customizable, stable platforms for stage-specific and tissue-targeted interventions, broadening the scope of successful in utero treatments. Collectively, these advances in prenatal diagnostics and therapeutic strategies present an opportunity to address congenital disorders at their origin, significantly improving longterm health outcomes and quality of life by intervening at the earliest stages of development.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"47 ","pages":"Article 201527"},"PeriodicalIF":0.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145925112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}