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{"title":"Integrated case–control and in silico analysis of DNA double-strand break repair gene variants (RAD51, XRCC2, XRCC3, XRCC4, and LIG4) for ovarian cancer susceptibility","authors":"Harshavardhani Canchi Sistla ,&nbsp;Arun Seshachalam ,&nbsp;Krishna Kumar Rathnam ,&nbsp;Taruna Rajagopal ,&nbsp;Srikanth Talluri ,&nbsp;Subaranjana Saravanaguru Vasanthi ,&nbsp;Nageswara Rao Dunna","doi":"10.1016/j.gene.2025.149989","DOIUrl":"10.1016/j.gene.2025.149989","url":null,"abstract":"<div><div>The contribution of low-penetrance DNA repair genes (DRGs) to ovarian cancer (OC) risk remains poorly understood. Variants in homologous recombination repair (HRR) and non-homologous end joining (NHEJ) pathway genes may influence genomic stability and modulate OC susceptibility. This population-based case–control study (474 subjects; 237 OC patients and 237 controls) evaluated polymorphisms in <em>RAD51, XRCC2, XRCC3</em> (HRR), and <em>XRCC4, LIG4</em> (NHEJ) to assess their role in OC predisposition. Genotyping was performed using PCR-RFLP, and logistic regression estimated risk associations. Multifactor Dimensionality Reduction (MDR) analysis examined SNP–SNP interactions, while <em>in silico</em> tools and electrostatic surface mapping predicted structural and functional effects. Significant associations were observed for <em>RAD51</em> (rs1801320), where individuals with the mutant CC genotype showed a 2.8-fold higher OC risk (OR = 2.85; 95 % CI = 1.15–7.06; p = 0.049), and the CT genotype of <em>LIG4</em> (rs1805388) conferred a 1.85-fold increased risk (OR = 1.85; 95 % CI = 1.11–3.07; p = 0.0097). Conversely, CT genotype carriers of <em>XRCC3</em> (rs861539) exhibited reduced OC risk (OR = 0.49; 95 % CI = 0.32–0.75; p = 0.003). <em>XRCC2</em> and <em>XRCC4</em> showed no significant associations. However, <em>XRCC2</em> variants correlated with tumor grade and menopausal status, and <em>XRCC3</em> with tumor histology. MDR analysis revealed strong interactions between <em>XRCC3</em> and <em>RAD51</em>, followed by combinations involving <em>XRCC2</em>, suggesting synergistic HRR gene effects. <em>In silico</em> predictions indicated XRCC2 R188H is destabilizing, XRCC3 T241M has mixed effects, and LIG4 T9I is stabilizing. Overall, <em>RAD51</em> and <em>LIG4</em> polymorphisms may contribute to OC susceptibility in South Indian women. Larger, multi-center studies are warranted to validate these findings and explore their potential as predictive biomarkers for OC.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"983 ","pages":"Article 149989"},"PeriodicalIF":2.4,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145882812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case report and literature review of neurodevelopmental syndrome linked to DOT1L variants","authors":"Aurélien Caux ,&nbsp;Florence Jobic ,&nbsp;Boris Keren ,&nbsp;Alexis Billes ,&nbsp;Virginie Magry ,&nbsp;Anaïs L’Haridon ,&nbsp;Walaa Darwiche ,&nbsp;Guillaume Jedraszak ,&nbsp;Gilles Morin","doi":"10.1016/j.gene.2025.149987","DOIUrl":"10.1016/j.gene.2025.149987","url":null,"abstract":"<div><h3>Introduction</h3><div>The <em>DOT1L</em> gene encodes a histone lysine methyltransferase that has the distinctive characteristic of being composed of a DOT1 catalytic domain that targets lysine 79 of the core globular domain of histone H3. <em>DOT1L</em> missense variants have recently been implicated in an autosomal dominant inheritance syndrome with developmental delay and congenital anomalies in postnatal cohorts. We report the twenty-sixth patient with this disorder.</div></div><div><h3>Methods</h3><div>Trio genome sequencing (GS) was performed in a patient with developmental delay.</div></div><div><h3>Results</h3><div>Clinical examination showed a predominant global developmental delay affecting language, with cerebral abnormalities visible on magnetic resonance imaging, hypotonia, and ophthalmological and musculoskeletal abnormalities. GS revealed a <em>de novo</em> heterozygous missense variant in exon 3 of <em>DOT1L</em> (c.161C &gt; T; p.(Ala54Val)), which is reported for the first time as the cause of developmental delay and congenital anomalies.</div></div><div><h3>Discussion</h3><div>Among the 26 reported patients, 23 have missense variants, two have truncating variants, and one has an in-frame deletion. The mode of transmission is predominantly <em>de novo</em>. Current studies indicate multiple pathogenic mechanisms underlying DOT1L-related disorder, including both gain-of-function and loss-of-function effects, underscoring the complexity of the disease etiology. Although the gene exhibits intolerance to loss-of-function variants, a considerable number of truncating variants are observed in control populations, suggesting incomplete penetrance and heterogeneity in the phenotypic expression of DOT1L-associated disorder. No phenotype-genotype correlation could be established. Among reported patients, including ours, the most consistent clinical manifestations are global developmental delay, predominantly affecting language and behavior, and possibly distinctive facial features.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"983 ","pages":"Article 149987"},"PeriodicalIF":2.4,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145870010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Organelle genome analysis reveals adaptation and conservation in endangered tree Phoebe chekiangensis","authors":"Ju Tang ,&nbsp;Ying-Feng Hu ,&nbsp;Jian-Wen Shao ,&nbsp;Zhi-Zhong Li","doi":"10.1016/j.gene.2025.149970","DOIUrl":"10.1016/j.gene.2025.149970","url":null,"abstract":"<div><div><em>Phoebe chekiangensis</em>, a nationally protected tree endemic to southeastern China, is of high ecological and economic value but lacks genomic resources for conservation and evolutionary studies. In this study, we assembled its complete organelle genomes, including a circular mitogenome of 864,971 bp and a plastome of 154,460 bp. The mitogenome is enriched in dispersed and simple sequence repeats, consistent with extensive structural rearrangements across Lauraceae, whereas coding regions (over 80 % similarity) remain largely collinear under strong functional constraints. We identified 31 mitochondrial plastid DNA sequences (26,890 bp; 3.11 % of the mitogenome), including five intact plastid protein-coding genes (PCGs) and 14 tRNAs, reflecting frequent plastid-to-mitochondrion transfers that may restore missing tRNAs and enhance genome variability. RNA editing analysis revealed 71 mitochondrial and 13 plastid sites, with <em>cox1</em> harboring the most, suggesting post-transcriptional modification of respiratory genes that could contribute to stress tolerance. Comparative analyses showed that plastid PCGs evolve faster than mitochondrial PCGs, and <em>atp6</em> displayed a signal of positive selection, potentially linked to adaptive adjustments in ATP synthase function and respiratory efficiency. Phylogenetic analyses based on organelle genomes confirmed the monophyly of Lauraceae but revealed little topological conflicts, likely reflecting lineage-specific substitution-rate heterogeneity. In conclusion, our results provide new insights into the dynamics of organelle genome evolution and establish valuable genomic resources for the conservation and molecular systematics of <em>P. chekiangensis</em> and Lauraceae.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"982 ","pages":"Article 149970"},"PeriodicalIF":2.4,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145832854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic and metabolomic insights into the oxygen adaptation mechanisms of Enterococcus faecalis YN771","authors":"Shengting Zhang ,&nbsp;Sha Zhao ,&nbsp;Lijuan Liu ,&nbsp;Huili Tao ,&nbsp;Jinmei Chai ,&nbsp;Yani Ju ,&nbsp;Chengqian Dong ,&nbsp;Yunlin Wei","doi":"10.1016/j.gene.2025.149985","DOIUrl":"10.1016/j.gene.2025.149985","url":null,"abstract":"<div><div><em>Enterococcus faecalis</em> is a facultative anaerobe often associated with persistent infections. It can rapidly adapt and grow in environments with varying oxygen levels (aerobic, microaerobic, hypoxic, and anaerobic), making it a major pathogen responsible for refractory periapical periodontitis. The study investigated the fatty acid content and its variations in <em>Enterococcus faecalis</em> strain YN771 under different oxygen concentrations. Subsequently, transcriptomics and metabolomics were combined to characterize the underlying mechanisms. The results showed that YN771 exhibited altered transcriptional and metabolomic profiles when exposed to different oxygen levels. These changes highlighted the oxygen adaptation and regulatory mechanisms of YN771, including sulfur metabolism, glutathione metabolism, glutamate metabolism, pyruvate metabolism, tricarboxylic acid cycle, peptidoglycan biosynthesis, and fatty acid biosynthesis regulation. Additionally, the study examined the expression changes of virulence factors in YN771 under different oxygen levels, which are also regulated by quorum sensing. This research comprehensively explores the metabolic regulation of YN771 under varying oxygen levels and analyzes key enzyme genes and virulence factors involved in its oxygen response regulation, providing mechanistic insights for developing therapeutic strategies against this notorious pathogen.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"982 ","pages":"Article 149985"},"PeriodicalIF":2.4,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PRDM14 promotes the bovine somatic stem cell reprogramming through enhancing oxidative phosphorylation at the initial stage","authors":"Qingqing Wei ,&nbsp;Wenhui Li ,&nbsp;Guina Cui ,&nbsp;Yiliang Xu ,&nbsp;Shaorong Gao","doi":"10.1016/j.gene.2025.149978","DOIUrl":"10.1016/j.gene.2025.149978","url":null,"abstract":"<div><div>Bovine induced pluripotent stem cells (biPSCs), which can be obtained through somatic cells reprogramming have multiple potential applications in human disease, regeneration medicine and biotechnical animal breeding. However, the low reprogramming efficiency and poorly exploration of the mechanism underlying the somatic cells reprogramming in cattle restricted the applications of biPSCs. Here, we reported the transcription factor PR-domain containing protein 14 (<em>PRDM14</em>) was highly expressed in bovine fetal testis and intestine. And the expression of <em>PRDM14</em> showed the lowest level in bovine embryonic fibroblasts (BEF), increased on day 3 and day 18, and finally reached the highest level in induced pluripotent stem cells (iPSCs) during the reprogramming induced by <em>OCT4</em>, <em>SOX2</em>, <em>KLF4</em> and <em>MYC</em> (OSKM). In a gain-of-function assay, we showed that <em>PRDM14</em> was able to enhance the efficiency of reprogramming from BEF in conjunction with bovine OSKM. While, silencing of <em>PRDM14</em> inhibited the reprogramming efficiency of BEF. The bovine iPSCs derived from OSKM plus <em>PRDM14</em> displayed normal karyotype, expressed pluripotent markers and could differentiated into three germ layers in vitro. Transcriptome analysis of cells at the early, median and late reprogramming stages revealed that several genes involved in oxidative phosphorylation (OXPHOS) are upregulated on day 3 when OXPHOS burst occurs, while downregulated on day 15 when OXPHOS transmits to glycolysis, by ectopic expression of <em>PRDM14</em>. RT-qPCR and ATP content detection further confirmed that <em>PRDM14</em> could improve somatic cells reprogramming by enhancing OXPHOS at the early stage. Additionally, forced expression of <em>PRDM14</em> in OSKM-induced biPSCs showed that it upregulates the expression of key pluripotency gene <em>NANOG</em> but downregulates <em>LIN28</em>, DNA methylation genes <em>DNMT1</em>/<em>3B</em> and DNA demethylation genes <em>TET1</em>/<em>2</em>/<em>3</em>. Altogether, our study uncovers <em>PRDM14</em> exemplifies a key transcription factor required for the reacquisition of pluripotency in bovine somatic cells and the maintenance of bovine iPSCs identity.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"982 ","pages":"Article 149978"},"PeriodicalIF":2.4,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145833363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro expression and seroreactivity of Toxoplasma gondii GRA1 protein encoded by unmodified and nucleoside-modified mRNA constructs","authors":"Mehmet Nadir Şahinci ,&nbsp;Mert Döşkaya ,&nbsp;Muhammet Karakavuk ,&nbsp;Seren Kaplan ,&nbsp;Gizem Mutlu ,&nbsp;Tuğçe Gizem Perçin ,&nbsp;Sedef Erkunt Alak ,&nbsp;Özlem Günay-Esiyok ,&nbsp;Aytül Gül Mete ,&nbsp;Aysu Değirmenci Döşkaya ,&nbsp;Ayşe Gülten Kantarcı ,&nbsp;Adnan Yüksel Gürüz ,&nbsp;Hüseyin Can","doi":"10.1016/j.gene.2025.149965","DOIUrl":"10.1016/j.gene.2025.149965","url":null,"abstract":"<div><div>Toxoplasmosis is an infectious parasitic disease caused by <em>Toxoplasma gondii</em>, with a global seroprevalence estimated to affect more than one-third of the human population. <em>T. gondii</em> can be a serious health concern for pregnant women and immunocompromised patients. Currently, there is no effective and safe vaccine for humans. However, mRNA technology is a promising platform to develop efficient and safe vaccines against toxoplasmosis. Therefore, we designed nucleoside-modified and unmodified mRNA vaccine transcripts expressing <em>T. gondii</em> recombinant GRA1 protein and analyzed their <em>in vitro</em> protein expression profile as well as potential immunogenicity using IFAT, Western blot, and ELISA. Moreover, to compare translational efficiency, poly-A tail was extended with an extra ∼150 bp in addition to the existing ∼120 bp poly-A tail in two distinct mRNA designs. The results showed that all four mRNA constructs expressed rGRA1 protein in HEK293T cells. However, mRNA constructs with extended poly-A tails exhibited reduced expression level of rGRA1 protein compared to other mRNA vaccine transcripts. Additionally, unmodified mRNA construct with or without extended poly-A tail yielded significantly higher protein expression compared to nucleoside-modified mRNA constructs through ELISA using anti-polyhis antibody (P&lt;0.05). Western blot showed that rGRA1 protein expressed by all four mRNA constructs reacted strongly with <em>T. gondii</em> IgG seropositive mice sera. Furthermore, ELISA revealed that rGRA1 proteins derived from unmodified and nucleoside-modified mRNA constructs formed significantly stronger immune complexes with <em>T. gondii</em> IgG antibodies compared to negative controls (P&lt;0.05). These data suggest that both unmodified and nucleosidemodified mRNA constructs expressing rGRA1 protein have potential as vaccine candidates and warrant further investigation for development of an mRNA-based vaccine against toxoplasmosis. However, encapsulation of the produced mRNA constructs in LNPs and <em>in vivo</em> studies are required to validate these preliminary results.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"982 ","pages":"Article 149965"},"PeriodicalIF":2.4,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginsenoside Rg1 delays chronological aging in a yeast model via SSE1-Mediated mitophagy","authors":"Ze Yao ,&nbsp;Ming Lu ,&nbsp;Chunshuang Li ,&nbsp;Xiang Li ,&nbsp;Hui Shang ,&nbsp;Songtao Bie","doi":"10.1016/j.gene.2025.149986","DOIUrl":"10.1016/j.gene.2025.149986","url":null,"abstract":"<div><div>Ginsenoside Rg1 (Rg1), an active compound in <em>Panax ginseng</em> C. A. Meyer (ginseng), has shown potential to ameliorate age-related cell damage and extend lifespan in multiple model organisms. However, the precise molecular mechanisms of its anti-aging effects remain unclear. In this study, we explore the anti-aging mechanisms of ginsenoside Rg1, focusing on its impact on mitophagy in <em>Saccharomyces cerevisiae</em>. Using propidium iodide staining, we found that Rg1 extends the chronological lifespan (CLS) of yeast cells. Further analyses revealed that Rg1 enhances mitochondrial function and antioxidant capacity in yeast cells by inducing mitophagy. Moreover, RNA-Seq and bioinformatics analyses identified the molecular chaperone <em>SSE1</em> as a key target of Rg1. <em>SSE1</em> knockout strain demonstrated that Rg1 enhances mitochondrial function and antioxidant capacity through <em>SSE1</em>-dependent mitophagy, thereby extending cell lifespan. Collectively, we concluded that Rg1 exerts its anti-aging effects through <em>SSE1</em>-mediated mitophagy. This study advances our understanding of Rg1-mediated mitophagy and mitochondrial regulation via <em>SSE1</em>, offering a foundation for the rational design of targeted anti-aging treatments.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"982 ","pages":"Article 149986"},"PeriodicalIF":2.4,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel tRNA-derived fragment tRF-Val-CAC-008 as a diagnostic biomarker and pyroptosis regulator in LSCC","authors":"Hongxia Deng ,&nbsp;Dong Ye ,&nbsp;Shijie Qiu ,&nbsp;Shuang Ye ,&nbsp;Chongchang Zhou ,&nbsp;Shuai Fang ,&nbsp;Yuna Zhang ,&nbsp;Shanshan Gu","doi":"10.1016/j.gene.2025.149967","DOIUrl":"10.1016/j.gene.2025.149967","url":null,"abstract":"<div><h3>Objective</h3><div>Laryngeal cancer is one of the most common malignant tumors of the head and neck, with laryngeal squamous cell carcinoma (LSCC) being the most significant pathological type. Transfer RNA-derived fragments (tRFs) fragments have been implicated in tumor progression through diverse regulatory mechanisms. This study examined the diagnostic value and role of tRF-Val-CAC-008 in LSCC.</div></div><div><h3>Methods</h3><div>Levels of tRF-Val-CAC-008 were quantified in LSCC tissues, plasma, saliva, and cells using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The diagnostic value of tRF-Val-CAC-008 was then assessed using the receiver operating characteristic (ROC) curve. LSCC cells were transfected with mimics or inhibitors of tRF-Val-CAC-008, which increased or decreased its level accordingly. Cell proliferation was evaluated using EdU and the cell counting kit-8 (CCK-8) assays. The level of lactate dehydrogenase (LDH) in LSCC cells was measured using an LDH release assay. Pyroptosis-associated proteins were analyzed by Western blotting (WB).</div></div><div><h3>Results</h3><div>tRF-Val-CAC-008 exhibited significantly higher expression levels in LSCC tissues, plasma and saliva. This higher expression correlated with its pro-proliferative effects and suppression of pyroptosis observed in vitro. In LSCC cells, tRF-Val-CAC-008 mimics promoted cell proliferation and reduced LDH secretion. The expression of gasdermin E (GSDME) and caspase-3 proteins was also decreased by tRF-Val-CAC-008 mimics, which in turn regulated pyroptosis. The ROC curves suggest that combined plasma and saliva tRF-Val-CAC-008 can serve as a diagnostic marker to distinguish LSCC patients from healthy participants.</div></div><div><h3>Conclusions</h3><div>The study concluded that tRF-Val-CAC-008 could act as a diagnostic marker for LSCC; it promotes tumor growth by suppressing pyroptosis and promoting cell proliferation.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"982 ","pages":"Article 149967"},"PeriodicalIF":2.4,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145793714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel candidate missense variant in the catalytic domain of USP26 associated with asthenoteratozoospermia","authors":"Seyedeh Zahra Mousavi ,&nbsp;Masomeh Askari ,&nbsp;Ken McElreavey ,&nbsp;Anu Bashamboo ,&nbsp;Najmeh Salehi ,&nbsp;Mandana Rastari ,&nbsp;Zeynab Rokhsattalab ,&nbsp;Bahram Mohammad Soltani ,&nbsp;Mehdi Totonchi","doi":"10.1016/j.gene.2025.149945","DOIUrl":"10.1016/j.gene.2025.149945","url":null,"abstract":"<div><h3>Introduction</h3><div>Teratozoospermia, characterized by abnormal sperm morphology, is a significant factor contributing to the male infertility. Deubiquitinating enzymes play a crucial role in controlling protein synthesis and degradation during spermatogenesis.</div></div><div><h3>Methods</h3><div>Whole exome sequencing (WES) and the following insilico analysis were performed to detect the associated variant with asthenoteratozoospermia in a consanguineous Iranian family with two affected brothers.</div></div><div><h3>Results</h3><div>WES identified a novel candidate hemizygous missense mutation (chrX-132161044 T &gt; G:NM_031907.2:c.1205A &gt; C, p.Asn402Thr) in the catalytic domain of the <em>USP26</em> (Ubiquitin-Specific Peptidase 26) deubiquitinating enzyme in two affected siblings. The <em>USP26</em> encodes a testis-specific deubiquitinating enzyme which is necessary for normal spermatogenesis and may influence male fertility. The mutation changes asparagine 402 (N) into threonine (T) and was co-segregated with phenotype in other available family members. In-silico predictions indicate that the N402T change not only leads to the absence of <em>a</em> hydrogen bond between the mutant N402T and F430 residues but also causes a reduction in <em>USP26</em> protein stability, potentially resulting in defects in <em>USP26</em> enzymatic activity.</div></div><div><h3>Conclusions</h3><div>Our findings support a potential role for <em>USP26</em> variants contributing to asthenoteratozoospermia.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"982 ","pages":"Article 149945"},"PeriodicalIF":2.4,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145803957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction notice to “Association of polymorphisms in the interleukin-4 gene with response to hepatitis B vaccine and susceptibility to hepatitis B virus infection: a meta-analysis” [Gene 525 (2013) 35–40]","authors":"Wei Cui,&nbsp;Cui-Ming Sun,&nbsp;Bao-Cheng Deng,&nbsp;Pei Liu","doi":"10.1016/j.gene.2025.149947","DOIUrl":"10.1016/j.gene.2025.149947","url":null,"abstract":"","PeriodicalId":12499,"journal":{"name":"Gene","volume":"981 ","pages":"Article 149947"},"PeriodicalIF":2.4,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}