Journal of Gene Medicine最新文献

{"title":"Artificial Intelligence for Predictive Modeling in CRISPR/Cas9 Gene Editing: a Survey of Methods and Design Strategies","authors":"Jay Patel,&nbsp;Dhruvi Patel,&nbsp;Aanal Raval","doi":"10.1002/jgm.70061","DOIUrl":"10.1002/jgm.70061","url":null,"abstract":"<div>\u0000 \u0000 <p>Ongoing developments in genome editing most notably the continued evolution of CRISPR-Cas systems and their orthogonal or modified counterparts have substantively altered both experimental and applied practices in biomedicine, agriculture, and therapeutic design. More recently, the systematic incorporation of artificial intelligence and machine learning methodologies has augmented the specificity, throughput, and explanatory capacity of genome-editing workflows, thereby refining the prediction of on-target efficiencies, the appraisal of off-target liabilities, and the tailoring of molecular therapeutic configurations. The present contribution offers an integrative survey of these computational developments, emphasizing (i) predictive algorithms, (ii) machine-learning and deep-learning frameworks, (iii) data-centric procedural strategies, and (iv) dedicated applications in oncology, neurology, rare-disease research, and precision-medicine contexts. Throughout, we evaluate architectural choices, sequence-encoding representations, and lingering dataset-related biases, while additionally addressing current constraints concerning model interpretability, ethical viability, and the procedural prerequisites for clinical translation. Moreover, we advance a structured taxonomy that organizes AI-mediated genome-editing approaches according to methodological lineage and functional scope, and we delineate extant research lacunae. By combining these elements, we supply a prospective assessment of the means by which artificial intelligence might be further leveraged to support secure, efficacious, and equitably accessible genome engineering outcomes.</p>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 12","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145716837","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":"miRNAs in Erdheim-Chester Disease: A Paradigm of Multisystem Histiocytosis","authors":"Mohamed Hemdan,&nbsp;Reda M. Mansour,&nbsp;Hebatallah Ahmed Mohamed Moustafa,&nbsp;Reem K. Shahin,&nbsp;Akram N. Salah,&nbsp;Manar Mohammed El Tabaa,&nbsp;Mai A. Abd-Elmawla,&nbsp;Nehal I. Rizk,&nbsp;Osama A. Mohammed,&nbsp;Sherif S. Abdel Mageed,&nbsp;Hanan A. Rizk,&nbsp;Ahmed S. Doghish","doi":"10.1002/jgm.70062","DOIUrl":"10.1002/jgm.70062","url":null,"abstract":"<div>\u0000 \u0000 <p>Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis identified in the early 20th century. ECD primarily affects adults and is characterized by systemic infiltration of foamy macrophages. ECD can infiltrate the bones, skin, heart, and central nervous system, causing various symptoms. Limited targeted treatments, immunotherapy, and chemotherapy options underscore the need for tailored approaches to this complex disorder. Recent studies have highlighted the role of microRNAs (miRNAs) as critical regulators of gene expression involved in various pathophysiological processes, including inflammation and immune responses. Likewise, ECD patients exhibited abnormal expression of miRNAs that can disrupt immunological checkpoints and histiocyte activity, leading to ECD histiocyte proliferation and survival. This review addresses the emerging evidence regarding the involvement of miRNAs in ECD, focusing on their potential as biomarkers for diagnosis and prognosis and their role in modulating the disease's inflammatory pathways. Understanding the specific miRNA profiles in ECD could provide insights into disease mechanisms and pave the way for targeted therapeutic strategies. Future research should elucidate the precise functions of miRNAs in ECD and their potential clinical applications.</p>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 12","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145671019","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":"Ferroptosis-Related Gene SAT1 Contributes to Immune Responses in Acute Pancreatitis","authors":"Kena Zhou,&nbsp;Congbo Cai,&nbsp;Rong Wan,&nbsp;Xingpeng Wang","doi":"10.1002/jgm.70063","DOIUrl":"10.1002/jgm.70063","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Ferroptosis and immune responses are catching more and more attention in inflammatory diseases. However, the specific function and mechanism of the popular ferroptosis-related gene SAT1 in acute pancreatitis (AP) still remain unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Differentially expressed genes (DEGs) and the Weighted Gene Co-Expression Network Analysis (WGCNA) were integrated to screen the core gene set related to AP. The characteristic gene was identified through three machine learning algorithms (LASSO, SVM-REF, and RF). Experimental approaches were performed to validate the findings by using qRT-PCR and immunohistochemistry (IHC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Machine learning combined with bioinformatics determined that the ferroptosis gene SAT1 was the key regulatory gene of AP. The expression level of SAT1 was positively correlated with the severity of AP (<i>p</i> &lt; 0.05), which was also involved in immune functions. Experiments in vivo and in vitro validated that SAT1 was significantly upregulated in murine AP models (<i>p</i> &lt; 0.01). Knockdown of SAT1 could alleviate inflammation responses by reducing IL1<i>β</i> and IL6, especially TNF<i>α</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>SAT1 is elevated in AP, serving as a potential diagnostic and prognostic biomarker. Down regulation of SAT1 can decrease the release of inflammatory factors. We identified SAT1 as a potential therapeutic target for AP.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 12","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145671065","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":"THBS1 Contributes to Chemoresistance in Ovarian Clear Cell Carcinoma via Promoting Epithelial–Mesenchymal Transition","authors":"Dongdong Ye,&nbsp;Yunyun Liu,&nbsp;Aoshuang Cheng,&nbsp;Dongdong Xu,&nbsp;Chuying Huo,&nbsp;Xibo Zhao,&nbsp;Suen Wai Pang,&nbsp;Chunxian Huang,&nbsp;Lijuan Wang,&nbsp;Shaodan Lin,&nbsp;Huaiwu Lu","doi":"10.1002/jgm.70058","DOIUrl":"https://doi.org/10.1002/jgm.70058","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Ovarian clear cell carcinoma (OCCC) is prone to primary platinum resistance and has a poor prognosis in advanced stages. Understanding the mechanisms underlying chemoresistance is essential to improving treatment outcomes. This study aimed to identify and validate molecular targets linked to platinum sensitivity in OCCC and explore their clinical and biological relevance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The mRNA sequencing was performed on fresh-frozen tumor tissues from six OCCC patients (three platinum-resistant and three platinum-sensitive). Differentially expressed genes (DEGs) were identified using edgeR and DESeq2. A random forest model ranked candidate genes by their predictive value, and prognostic associations with progression-free survival (PFS) and overall survival (OS) were assessed via the database of the Cancer Science Institute of Singapore (CSIOVDB). The protein expression of THBS1 was compared between groups using immunohistochemistry. Functional effects of THBS1 knockdown were assessed through CCK-8, colony formation, wound healing, transwell assays, and tube formation assays using HUVECs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 1592 DEGs were identified, with 43 overlapping with GSEA-defined platinum resistance pathways. Enrichment analysis indicated significant enrichment of cancer-related signaling pathways and biological processes were enriched in the platinum-resistant group. Gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) highlighted the platelet-associated biological processes and immune relative pathway. The immune infiltration landscape indicated a prominent immunosuppressive microenvironment in the platinum-resistant group. THBS1 ranked highly in the random forest model and was associated with shorter PFS (<i>p</i> = 0.0012) and OS (<i>p</i> = 0.0046) in CSIOVDB analysis. Immunohistochemistry confirmed elevated THBS1 expression in the platinum-resistant group (<i>p</i> &lt; 0.0001). In vitro, THBS1 knockdown reduced cell migration, invasion, angiogenesis, and cisplatin resistance. It also downregulated E-cadherin while upregulating N-cadherin and vimentin, suggesting EMT pathway involvement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>THBS1 promotes platinum resistance in OCCC through EMT activation and may serve as a prognostic biomarker and therapeutic target.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 12","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626221","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":"A-to-I RNA Edited miR-605-3p Has a Heightened Anti-Tumor Effect in Colorectal Cancer Through Modulating Immune Infiltration Mediated by CDK6","authors":"Xi-Zhong Cai,&nbsp;Dan-Yang Li,&nbsp;Kuang Gou,&nbsp;Shuai Wang,&nbsp;Chu-Yang Guo","doi":"10.1002/jgm.70060","DOIUrl":"https://doi.org/10.1002/jgm.70060","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Adenosine-to-inosine (A-to-I) RNA editing represents a prevalent post-transcriptional modification with profound implications for human diseases, particularly cancer. In colorectal cancer (CRC), the specific roles of A-to-I editing events remain inadequately understood. This study sought to elucidate the role and underlying mechanism of edited miR-605-3p in CRC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The expression levels of miRNA and gene were assessed using RT-qPCR, Western blotting, and immunohistochemistry. Tumor cell metastasis and proliferation were evaluated through Transwell and CCK-8 assays, while flow cytometry was utilized to examine tumor cell apoptosis and CD8+ T cell populations. The relationship between gene and miRNA was confirmed via a dual-luciferase reporter assay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In CRC tissues, the A-to-I RNA editing level of miR-605-3p was found to be elevated, which correlated with favorable clinical outcomes and prognosis in CRC patients. The ADAR2 enzyme is responsible for the overediting of miR-605-3p in CRC. Functionally, the wt-miR-605-3p inhibited cell viability and metastasis of CRC, and its anti-tumor efficacy of miR-605-3p was enhanced by A-to-I RNA editing. Mechanically, the edited-miR-605-3p directly targets CDK6, in contrast to the wt-miR-605-3p. Overexpression of CDK6 was observed to promote CRC cell proliferation and metastasis by impeding CD8+ T cell immune infiltration. MiR-605-3p overediting inhibited CRC tumor growth in vivo by downregulating CDK6.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The A-to-I RNA edited miR-605-3p demonstrates a more potent anti-tumor effect in CRC by modulating CD8+ T cell immune infiltration mediated by CDK6. This study unveils edited miR-605-3p as a potential prognostic biomarker and highlights the ADAR2-miR-605-3p axis as a novel therapeutic target for CRC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 12","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145601176","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":"The Role of the CLIC/GEEC Endocytic Pathway for Mechanophysical Transfection of DNA","authors":"Sean Weaver,&nbsp;Emran O. Lallow,&nbsp;Kelly Kyker-Snowman,&nbsp;Nandita C. Jhumur,&nbsp;Melissa Gulley,&nbsp;Christine C. Roberts,&nbsp;David I. Shreiber,&nbsp;Hao Lin,&nbsp;Joel N. Maslow","doi":"10.1002/jgm.70059","DOIUrl":"https://doi.org/10.1002/jgm.70059","url":null,"abstract":"<p>The clathrin-independent carriers/glycosylphosphatidylinositol-attached protein-enriched endosomal compartments (CLIC/GEEC) pathway is a clarithin- and dynamin-independent endocytic pathway. CLIC/GEEC-mediated endocytosis is a large-capacity, rapid-acting process that is utilized by cells for bulk uptake of nutrients and membrane-anchored cargo and for homeostatic maintenance of membrane tension. Here, we present a brief overview of this pathway, including its known molecular mechanisms, inhibitors, activity in different cell types, and its potential relevance in mechanophysical DNA transfection.</p>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 12","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jgm.70059","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145601141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"YTHDF3 Promotes N6-Methyladenosine Modification of SOCS1 to Inhibit JAK1/STAT3 Pathway in the Pathogenesis of Preeclampsia","authors":"Shuang Sui,&nbsp;Xinchun Wang,&nbsp;Yanmei Zhang,&nbsp;Ying Huang","doi":"10.1002/jgm.70036","DOIUrl":"10.1002/jgm.70036","url":null,"abstract":"<div>\u0000 \u0000 <p>Preeclampsia (PE) is a common complication during pregnancy. Trophoblast cells are the main cell type of the placenta, and abnormalities in proliferation and differentiation cause anterior placental accretion and lead to the development of PE. This study will investigate the function and related mechanism of N6-methyladenosine (m⁶A) reader YTH N6-methyladenosine RNA binding protein F3 (YTHDF3) in PE and provide a rationale for the therapeutic treatment of PE. In the study, YTHDF3 and suppressor of cytokine signaling 1 (SOCS1) expression were significantly upregulated within PE placental tissue samples. <i>YTHDF3</i> knockdown promoted the capacity of hypoxia-treated trophoblast cells to proliferate, migrate, invade, and undergo epithelial-mesenchymal transition (EMT) and inhibited apoptosis. The JAK1/STAT3 pathway is aberrantly activated in trophoblast cells of PE. YTHDF3 binds m⁶A-modified <i>SOCS1</i> mRNA to enhance its stability and translation. <i>YTHDF3</i>/<i>SOCS1</i> promotes disease progression in PE by inhibiting the JAK1/STAT3 signaling pathway. In conclusion, YTHDF3 promotes the disease progression of PE by enhancing the m⁶A modification of <i>SOCS1</i> mRNA and suppressing the JAK1/STAT3 signaling pathway. YTHDF3 has been identified as an underlying target for the clinical treatment of PE.</p>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 11","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145598067","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":"A Pan-Cancer Analysis of the Oncogenic Role of YES Proto-Oncogene 1 (YES1) in Human Tumors","authors":"Ruohan Dou,&nbsp;Ling Han,&nbsp;Guanya Liu,&nbsp;Xianli Zhu,&nbsp;Zhengyao Yang,&nbsp;Pengfei Hu,&nbsp;Yuantao Su","doi":"10.1002/jgm.70046","DOIUrl":"10.1002/jgm.70046","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Numerous studies have underscored the oncogenic function of YES Proto-Oncogene 1 (YES1) in various tumors. However, the relationship between YES1 and different tumors in pan-cancer patients, based on extensive clinical data, remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Integrating data from bioinformatics platforms (TIMER2, GEPIA2, UALCAN, cBioPortal, UniProt, STRING, and DAVID), we systematically interrogated YES1 expression patterns across malignancies. Multidimensional assessments encompassing clinical outcomes, genetic alteration profiles, post-translational modifications, and immunocyte infiltration dynamics were performed. Pathway enrichment mapping was subsequently applied to delineate oncogenic signaling networks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Tumor-type-specific YES1 expression signatures demonstrated significant prognostic stratification capacity. Molecular profiling revealed some core pathological mechanisms: genomic instability hotspots, phosphoproteomic deregulation in malignancies, and CAF-dominated tumor microenvironment remodeling in mesenchymal neoplasms. Systems biology approaches further uncovered YES1-mediated coordination of hallmark cancer processes, particularly cancer-related signaling pathways and protein processing functions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This initial systematic pan-cancer investigation establishes YES1 as a pleiotropic oncogenic regulator, with mechanistic heterogeneity across tumor lineages. The multidimensional characterization provides a translational framework for developing lineage-specific therapeutic strategies targeting YES1 signaling networks.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 11","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145598012","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":"Genetic Relationship Between Menarche and Height in East Asians: Functional Role of LIN28B in Pubertal Timing and Growth","authors":"Ying-Ju Lin,&nbsp;Ju-Pi Li,&nbsp;Hou-Ren Chen,&nbsp;Ming-Kuem Lin,&nbsp;Cherry Yin-Yi Chang,&nbsp;Hsing-Fang Lu,&nbsp;Wen-Miin Liang,&nbsp;Jian-Shiun Chiou,&nbsp;Jai-Sing Yang,&nbsp;Chen-Hsing Chou,&nbsp;Ting-Hsu Lin,&nbsp;Chiu-Chu Liao,&nbsp;Shao-Mei Huang,&nbsp;I-Ching Chou,&nbsp;Te-Mao Li,&nbsp;Fuu-Jen Tsai","doi":"10.1002/jgm.70052","DOIUrl":"10.1002/jgm.70052","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Observational and genetic studies associate later menarche with greater height, but their causal relationship, shared genomic regions, and <i>LIN28B</i>'s role in puberty and growth remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted genetic correlation, bidirectional Mendelian randomization (MR), and local genetic correlation analyses between menarche timing and adult height in 309,507 East Asians from Taiwan Biobank (TWB), Biobank Japan (BBJ), and the Korean Genome and Epidemiology Study (KoGES). We also examined how <i>LIN28B</i> overexpression affects chondrocyte maturation and hypothalamic–pituitary–gonadal (HPG) axis activation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Later menarche showed a positive genetic correlation with taller stature in both BBJ (Rg = 0.200, <i>p</i> = 1.82 × 10⁻⁸) and KoGES (Rg = 0.211, <i>p</i> = 7.62 × 10⁻⁸) datasets. MR confirmed a bidirectional causal relationship, indicating that later menarche increased height (MR-weighted median: β = 0.103, <i>p</i> = 4.32 × 10⁻⁹), whereas taller stature delayed menarche (MR-PRESSO [outlier-corrected]: β = 0.174, <i>p</i> = 1.26 × 10⁻³). Local genetic correlation analysis revealed five genomic regions with significant positive associations (<i>p</i> &lt; 0.05/1664), including a critical locus on chromosome six harboring <i>LIN28B</i>, suggesting its important role in both traits. In vitro, <i>LIN28B</i> overexpression enhanced chondrocyte proliferation while inhibiting their differentiation and suppressed hypothalamic GnRH expression (<i>p</i> &lt; 0.05), suggesting its dual regulation of growth and puberty.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings demonstrate a bidirectional relationship between menarche timing and adult height in East Asians, highlight five shared genomic regions, and underscore <i>LIN28B</i>'s role in hormonal and chondrocyte activity as a potential regulator of pubertal timing and growth.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 11","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145589820","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":"De Novo Missense Variant in TP63 Gene: Insights on Clinical and Molecular Investigations","authors":"Jilong Chen,&nbsp;Xufeng Xi,&nbsp;Xiaoman Xu,&nbsp;Yao Lin","doi":"10.1002/jgm.70055","DOIUrl":"10.1002/jgm.70055","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aims to investigate the phenotypes, mutation types, and loci associated with <i>TP63</i>-related syndrome by focusing on an affected proband.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Employing a proband collection strategy, we identified a family presenting with <i>TP63</i>-related syndrome and performed thorough clinical evaluations on the proband and family members. We subsequently documented the phenotype, mutation type, and locus of the <i>TP63</i> gene, followed by Sanger DNA sequencing analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified a family affected by <i>TP63</i>-related syndrome. The proband, a young adult male, demonstrated congenital anodontia, hypohidrosis, sparse hair, and additional features characteristic of ectodermal dysplasia. Further clinical manifestations included left ear hearing impairment, cleft lip/palate, hypospadias, and syndactyly. Sequencing analysis revealed a missense nucleotide variant (c.184G&gt;C, p.Val62Leu) in exon 2 of the <i>TP63</i> gene. This variant was absent from established SNP databases and was not detected in other family members or unrelated healthy individuals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The family exhibits significant symptoms consistent with <i>TP63</i> syndrome. The identified missense mutation is preliminarily considered to be pathogenic.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 11","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12634139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145566483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}