Genes最新文献

{"title":"Comparison of Four Bisulfite Conversion Kits and Their Effects on DNA Methylation Detection and Age Prediction.","authors":"Monica Giuffrida, Claus Børsting, Vania Pereira","doi":"10.3390/genes17091100","DOIUrl":"10.3390/genes17091100","url":null,"abstract":"<p><p><b>Background/Objectives</b>: This study aimed to compare the performance of four commercial bisulfite conversion kits-the Premium Bisulfite Kit, the SuperMethyl™ Fast Bisulfite Conversion Kit, the SuperMethyl™ Max Bisulfite Conversion Kit, and the EZ DNA Methylation-Gold™ Kit (hereafter: Premium, Fast, Max, and Gold)-to evaluate their impact on the age prediction accuracy at different DNA input levels. <b>Methods</b>: Comparisons were performed using DNA extracted from blood samples and DNA methylation standards. Different inputs of DNA were tested (1-50 ng), and all samples were analyzed twice. After bisulfite treatment, 10 targets were amplified by PCR and sequenced on a MiSeq instrument. Performance was evaluated across several metrics: DNA yield after PCR, conversion efficiency, read depth and β-value reproducibility, β-value specificity, cost, and hands-on time. Furthermore, DNA methylation levels of age-associated CpGs on the 10 PCR fragments were investigated, and the accuracy of age predictions was determined. <b>Results</b>: No kit was superior in performance across all metrics. Higher post-PCR DNA concentrations and more robust and reproducible results, particularly at lower DNA inputs, were obtained after treatment with the Premium and Max kits. The amplicon concentrations, read depths, and reproducibility between duplicate determinations were significantly lower with 1 ng DNA input compared to inputs of 5-50 ng DNA. <b>Conclusions</b>: For forensic genetic age prediction purposes, the Max or Premium kits represented more suitable options for bisulfite conversion, whereas the Fast kit may be preferable in settings where sample quantity is not a limiting factor, and cost or throughput are the primary considerations.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of the Mitochondrial Genome Landscape in MSCs, iPSCs and iMSCs from Osteoarthritis Patients and Healthy Donors.","authors":"Vasileios Konteles, Ioanna Papathanasiou, Maria Tzetis, Eugenios Goussetis, Kostantinos Malizos, Aspasia Tsezou","doi":"10.3390/genes17091101","DOIUrl":"10.3390/genes17091101","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Osteoarthritis (OA) is strongly associated with mitochondrial dysfunction, oxidative stress, and the accumulation of mitochondrial DNA (mtDNA) alterations in several joint-associated cell types, including chondrocytes, synoviocytes, and mesenchymal stromal cells (MSCs). These alterations contribute to impaired cellular homeostasis and reduced regenerative potential. In this study, we systematically characterized mtDNA heteroplasmy and variant distribution across bone marrow MSCs, induced pluripotent stem cells (iPSCs) and induced MSCs (iMSCs) derived from OA patients and healthy donors. <b>Methods:</b> Ultra-deep mitochondrial genome sequencing was integrated with transcriptomic and miRNome analyses to investigate mitochondrial remodeling during cellular reprogramming, encompassing changes in mtDNA heteroplasmy, variant distribution, mtDNA copy number and associated transcriptomic adaptations of nuclear-encoded mitochondrial pathways. <b>Results:</b> OA-derived MSCs exhibited a markedly increased heteroplasmic burden, followed by decrease in mtDNA copy number and accumulation of non-synonymous variants, particularly within OXPHOS-related genes, including MT-ND1-5, MT-ATP8, MT-CO1, and MT-RNR1/2. Reprogramming into iPSCs and subsequent differentiation into iMSCs were associated with an increase in mtDNA copy number and a progressive reduction in heteroplasmic variants predicted to have pathogenic potential, including m.7913C>T and m.7821G>A, as well as substantial reduction in heteroplasmic variant burden within several mitochondrial genes, suggesting mitochondrial genome remodeling during cellular reprogramming. Multiomic analysis further revealed coordinated deregulation of mitochondrial-associated nuclear genes and ceRNA regulatory networks involving lncRNAs MEG3 and SNHG14, along with multiple mitochondria-related miRNAs. These findings suggest post-transcriptional regulations associated with mitochondrial adaptation in iMSCs <b>Conclusion:</b> Collectively, our findings suggest that cellular reprogramming is associated with mitochondrial genomic reorganization in the donor-matched cell populations examined. These exploratory observations support the utility of iMSCs as a relevant model for studying OA-associated mitochondrial alterations and as a potential tool for regenerative approaches in OA.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-Omics and Machine Learning Identify Immune-Linked Gene Signatures for LUAD Stratification.","authors":"Rakesh Arya, Viplov Kumar Biswas, Hemlata Shakya, Moumita Majumdar, Jong-Joo Kim","doi":"10.3390/genes17091096","DOIUrl":"10.3390/genes17091096","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Background&lt;/b&gt;: Lung adenocarcinoma (LUAD) is the most common subtype of non-small-cell lung cancer and is one of the leading causes of cancer-related deaths globally. Despite current developments, reliable biomarkers for effective diagnosis, prognosis, and patient stratification are still lacking. &lt;b&gt;Methods&lt;/b&gt;: We analyzed publicly available TCGA-LUAD and GEO datasets using integrative bioinformatics approaches, including differential gene expression, weighted gene co-expression network analysis (WGCNA), survival modeling, mutation profiling, immune cell infiltration scores, machine learning, and bulk-RNA and single-cell RNA sequencing. &lt;b&gt;Results&lt;/b&gt;: A total of 5581 deregulated genes were identified, with the turquoise module (298 genes) showing strong correlation with LUAD (Corr = -0.79, &lt;i&gt;p&lt;/i&gt; &lt; 2.2 × 10&lt;sup&gt;-308&lt;/sup&gt;). The integration of two analyses yielded 281 overlapping genes, out of which nine candidates (&lt;i&gt;ANO2&lt;/i&gt;, &lt;i&gt;CHIAP2&lt;/i&gt;, &lt;i&gt;CPED1&lt;/i&gt;, &lt;i&gt;DNASE1L3&lt;/i&gt;, &lt;i&gt;GSTM5&lt;/i&gt;, &lt;i&gt;HTR3C&lt;/i&gt;, &lt;i&gt;PRKCE&lt;/i&gt;, &lt;i&gt;SLC14A1&lt;/i&gt;, and &lt;i&gt;WNT3A&lt;/i&gt;) were selected via LASSO Cox regression to build a prognostic risk model. High-risk patients have significantly worse survival (log-rank &lt;i&gt;p&lt;/i&gt; = 0.0027). &lt;i&gt;CPED1&lt;/i&gt; exhibited the highest mutation frequency, with 41% of TCGA-LUAD samples harboring mutations. Among all &lt;i&gt;CPED1&lt;/i&gt; mutation events, missense mutations were the most common (47%). GSEA and KEGG analysis revealed significant enrichment of pathways such as nucleocytoplasmic transport, oxidative phosphorylation, protein processing in the endoplasmic reticulum, ribosome, and ribosome biogenesis in high-risk patients. Immune infiltration analysis indicated differences in immune cell infiltration scores between high- and low-immune-score groups, with M1 macrophages showing strong statistical correlation with aDC, monocytes, and CD4&lt;sup&gt;+&lt;/sup&gt; naïve T cells. Machine learning confirmed that the combined Enet+PLS model predicted &lt;i&gt;CPED1&lt;/i&gt; as a core predictor, and &lt;i&gt;CPED1&lt;/i&gt; was successfully validated in independent GEO datasets (GSE43458 and GSE31210), showing strong diagnostic accuracy (AUCs up to 0.98). Finally, single-cell RNA sequencing revealed that &lt;i&gt;CPED1&lt;/i&gt; was mostly expressed in fibroblasts and myeloid cells, with &lt;i&gt;CPED1&lt;/i&gt; significantly downregulated in LUAD compared with normal samples. &lt;b&gt;Conclusions&lt;/b&gt;: This study integrates multi-omics and machine learning to highlight &lt;i&gt;CPED1&lt;/i&gt; as a promising candidate biomarker, with potential diagnostic and prognostic relevance in LUAD. The nine-gene risk signature stratified patients by survival outcomes in the TCGA cohort. Genomic and immune analyses revealed features associated with the high-immune-score group. As the study is entirely computational and the prognostic model lacks external survival validation, these findings should be regarded as preliminary and hypothesis-generating, requiring future independent validation and functional studies to confirm the bi","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Evidence for Metabolites Mediated Causal Inference Between Gut Microbiota and Venous Thromboembolism.","authors":"Pin Huang, Wenxiao Wei, Ying Xiao, Qian Zhu","doi":"10.3390/genes17091098","DOIUrl":"10.3390/genes17091098","url":null,"abstract":"<p><p><b>Background</b>: More efficient and safe preventive treatments for venous thromboembolism (VTE) are warranted to decrease the incidence of hemorrhage. Emerging evidence has highlighted the pivotal role of the intestinal microbiota alterations and their metabolites in the pathophysiology of VTE process. However, the specific species involved the VTE process and the potential underlying mechanisms remain unclear. <b>Methods</b>: The causal relationships between 82 species and VTE were assessed using two-sample Mendelian Randomization (MR) analyses. Instrumental variables (F > 10) without horizontal pleiotropy were selected using the PhenoScanner and MR PRESSO global test. Subsequently, causal estimates were primarily derived using the inverse variance weighted method. The reliability of the results was further examined utilizing various sensitivity analyses, reverse MR analysis and multivariate MR analysis. Additionally, the potential mediated effects of gut microbiota-related metabolites were explored and replicated using the mediation MR analysis. Moreover, genome annotation and pathway enrichment analysis were conducted to investigate the role of <i>CAG-81 sp000435795</i> in the related metabolites metabolism. <b>Results</b>: We identified independent and positive causal effects of <i>CAG-81 sp000435795</i> and <i>CAG-877 sp000433455</i> on VTE, which remained robust across multiple sensitivity analyses. Mediation analysis further revealed that the causal effect of <i>CAG-81 sp000435795</i> on VTE risk was partially mediated by albumin, Omega-3 fatty acids and polyunsaturated fatty acids (PUFA), which were all validated in the replicated cohorts. Furthermore, <i>CAG-81 sp000435795</i> might participate in the metabolism of albumin and fatty acids. <b>Conclusions</b>: Our findings provide evidence supporting a causal role of <i>CAG-81 sp000435795</i> in the VTE pathogenesis and implicate microbes associated metabolites, albumin and Omega-3, as potential mediators.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Propionic Acidemia: An Ambispective Cohort Study on Phenotypic and Genotypic Characteristics at a Tertiary Center in Vietnam.","authors":"Diep Minh Quang, Chi Dung Vu, Khanh Ngoc Nguyen, Ngoc Lan Nguyen, Tran Thi Chi Mai, Nguyen Thi Thanh Huong, Do Thi Mo, Le Thi Phuong, Thinh Huy Tran, Nguyen Huu Tu, Ngo Xuan Khoa, Vu Viet Ha Vuong, Van Khanh Tran","doi":"10.3390/genes17091099","DOIUrl":"10.3390/genes17091099","url":null,"abstract":"<p><p><b>Background/objective</b>: Propionic acidemia (PA), an autosomal recessive metabolic disorder, is caused by biallelic pathogenic variants in the <i>PCCA</i> or <i>PCCB</i> genes. In Vietnam, molecular analyses of PA have been scarce. Hence, the objective of this study was to investigate the phenotypic and genotypic characteristics and clinical management of Vietnamese children with PA. <b>Methods</b>: An ambispective descriptive cohort study was conducted on 14 children who were diagnosed with PA at the Vietnam National Children's Hospital. Collected data encompassed clinical manifestations, biochemical profiles, imaging characteristics, genetic findings, clinical management, and outcomes. <b>Results</b>: Symptom onset within the cohort spanned the neonatal, early infantile, and early childhood periods, with a median age at onset of 7.50 months (range 0.33-34.00 months). The clinical phenotype was characterized by acute encephalopathy, accompanied by lethargy (64.3%), vomiting (57%), and seizures (43%). Even though all tested cases exhibited abnormal urinary organic acids and elevated propionylcarnitine (C3) concentration, other key laboratory findings comprised hyperammonemia (100%), metabolic acidosis (64%), and hematological alterations (64%). The study identified eight pathogenic or likely pathogenic <i>PCCB</i> variants and two variants of uncertain significance, with the c.1124C>T being the most frequently identified variant. This cohort had severe clinical outcomes, as neurodevelopmental impairment was observed in 79% of cases with a mortality rate of 43%. <b>Conclusions</b>: This study underscores the severe clinical and biochemical characteristics of PA in 14 Vietnamese children, reinforcing the necessity of early detection and comprehensive long-term care for PA patients. Furthermore, the identification of 10 <i>PCCB</i> variants, including the recurrent c.1124C>T, p.(Ala375Val) variant in our cohort, broadens the known <i>PCCB</i> variant spectrum.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling Circular and Messenger RNA Dynamics in Colorectal Tumorigenesis: Insights into Tissue Heterogeneity and MSI-MSS Tumor Distinction.","authors":"Sabine Vautier, Corentin Levacher, Florent Marguet, Edwige Kasper, Jean-Christophe Sabourin, Stéphanie Baert-Desurmont, Philippe Ruminy, Claude Houdayer","doi":"10.3390/genes17091091","DOIUrl":"10.3390/genes17091091","url":null,"abstract":"<p><strong>Background/objectives: </strong>Circular RNAs (circRNAs) are emerging regulators of genetic information that share the spliceosome biogenesis pathway with messenger RNAs (mRNAs), influencing their expression. There is an increasing body of evidence supporting their role in colorectal cancer (CRC) tumorigenesis. This study explored circRNAs in two distinct CRC tumorigenesis pathways: microsatellite instability (MSI) and microsatellite stability (MSS). We investigated competition between mRNA and circRNAs from their host genes, which could potentially disrupt normal gene regulation, and examined specific patterns of alterations in MSS and MSI tumors.</p><p><strong>Methods: </strong>Circular (circ) and linear (lin) exon-exon junctions were quantified using exon-specific probes targeting 48 genes involved in CRC predisposition and tumorigenesis processes. RNA was extracted from colorectal FFPE samples (stage 1 to 4 adenocarcinomas and adenomas). MSS tumors (MSS-TTs) and adjacent normal tissue (MSS-NT) were selected from 21 patients with a severe personal or family history of cancer. MSI tumors (MSI-TTs) and adjacent normal tissue (MSI-NT) were selected from 16 patients. Muscle content was also investigated as a potential confounding factor.</p><p><strong>Results: </strong>Principal component analysis distinguished NT from TT samples based on the sums of circular and linear junctions. CircRNA abundance was higher in samples with an elevated muscle content (Kruskal-Wallis test <i>p</i>-value = 0.034). Linear regression, adjusted for muscle content, showed significantly reduced global circRNA levels in tumors compared to in healthy tissues (MSI and MSS combined, <i>p</i>-value = 0.00268). In the MSS group, significant differences were observed between MSS-NT and MSS-TT in terms of circ/lin ratios and linear and circular junction counts for specific genes. MSI analysis revealed distinct gene profiles, with significant differences only in linear junction counts.</p><p><strong>Conclusions: </strong>Our results do not suggest competition between the circRNAs and mRNAs of the key oncogenic genes that we investigated, but they do reveal differences in circRNA/mRNA expression patterns within normal and tumor tissues.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Association Between Hyperketonemia and Reduced Circulating Hydrogen Sulfide in Children with Type 1 Diabetes, and Ketone Inhibition of Cystathionine-γ-Lyase mRNA Expression in Cultured Hepatocytes.","authors":"Sushil K Jain, Rajesh Parsanathan, Jeffrey Justin Margret, Neslihan Gungor, John A Vanchiere, Maroun J Mhanna, Robert McVie","doi":"10.3390/genes17091090","DOIUrl":"10.3390/genes17091090","url":null,"abstract":"<p><strong>Background: </strong>Hydrogen sulfide (H₂S) is known for its significant anti-inflammatory, antioxidant, and vasculoprotective properties. In diabetic patients, blood levels of H₂S are observed to be lower. Type 1 diabetic patients (T1D) often experience both hyperketonemia and hyperglycemia. Cystathionine-γ-lyase (CSE), an enzyme encoded by the <i>CTH</i> gene, is responsible for the biosynthesis of H₂S. However, it remains uncertain whether the downregulation of <i>CTH</i> genes by ketones is linked to reduced levels of H₂S.</p><p><strong>Objective: </strong>This study aims to test the hypothesis that ketones decrease <i>CTH</i> gene expression in cultured hepatocytes and that hyperketonemia negatively correlates with H₂S levels in T1D.</p><p><strong>Methods: </strong>Fasting blood samples were collected from children with T1D (<i>n</i> = 36) and age-matched healthy controls (<i>n</i> = 35), following written informed consent. Plasma levels of H₂S, 25(OH)VD, ketones, and inflammatory biomarkers were analyzed. To assess the effects of hyperglycemia and hyperketonemia on <i>CTH</i> gene expression, cultured hepatocytes were exposed to high glucose, acetoacetate, or β-hydroxybutyrate.</p><p><strong>Results: </strong>Blood levels of H₂S and 25(OH)VD were significantly lower in T1D patients compared to healthy controls. Plasma H₂S concentrations showed an inverse association with total ketones, BHB, acetoacetate, and MMP-9, while they were positively associated with HDL-cholesterol and 25(OH)VD. In cultured hepatocytes, exposure to acetoacetate and high glucose was linked to reduced <i>CTH</i> mRNA expression.</p><p><strong>Conclusions: </strong>Lower circulating H₂S concentrations are associated with hyperketonemia and inflammatory/metabolic abnormalities in children and adolescents with T1D. The <i>in vitro</i> findings suggest that high glucose and acetoacetate may affect <i>CTH</i> transcription; however, further studies measuring CSE protein, enzymatic activity, and H₂S production are necessary to clarify the underlying mechanism and establish causality.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Molecular Testing for Presumptive Genetic Eye Diseases.","authors":"Marisol Ibarra-Ramírez, Jibran Mohamed-Noriega, Joel Arenas-Estala, David Asael Rodríguez-Torres, Luis Daniel Campos-Acevedo, Marissa L Fernández-de-Luna","doi":"10.3390/genes17091092","DOIUrl":"10.3390/genes17091092","url":null,"abstract":"<p><p><b>Background</b>: Genetic eye diseases (GEDs) comprise a heterogeneous group of hereditary and de novo disorders that involve all ocular structures, including the retina, optic nerve, vitreous, anterior segment, and ocular development. Their marked clinical and genetic heterogeneity frequently delays diagnosis and access to genetic counseling, multidisciplinary management, and emerging gene-based therapies. Although ophthalmic deep phenotyping remains essential, we propose an approach that prioritizes genetic analysis, particularly in under-resourced healthcare settings with limited access to advanced imaging and electrophysiological tests. <b>Methods:</b> We conducted a retrospective observational study of 101 consecutive patients with suspected genetic eye diseases. All were evaluated at a tertiary referral center in northeastern Mexico between January 2020 and August 2023 through comprehensive ophthalmologic examination supplemented by optical coherence tomography, visual-field testing, and fundus photography when clinically indicated. All patients were offered early molecular testing while awaiting future tests, such as electrophysiological testing or further referral visits. Molecular testing consisted of an ophthalmology-focused next-generation sequencing multigene panel. <b>Results:</b> The primary outcome was molecular diagnostic yield. A clinically actionable molecular diagnosis was established in 45 patients, corresponding to an overall molecular diagnostic yield of 44.6%. A total of 165 variants were identified, including 70 pathogenic, 16 likely pathogenic, 43 variants of uncertain significance, and 36 likely benign variants. Usher syndrome was the most frequent molecular diagnosis (10/45, 22.2%), comprising nine patients with <i>USH2A</i>-associated Usher syndrome type 2 and one patient with <i>MYO7A</i>-associated Usher syndrome type 1B, followed by Stickler syndrome (8/45, 17.8%), oculocutaneous albinism (3/45, 6.7%), and Alström syndrome (2/45, 4.4%). Autosomal recessive disorders represented the predominant inheritance pattern (68.9%). <b>Conclusions:</b> Our findings support ophthalmology-focused multigene panels as an effective first-line diagnostic strategy for patients with suspected genetic eye diseases. Early molecular testing may shorten the diagnostic odyssey, optimize resource utilization, facilitate precision diagnosis and genetic counseling, and guide future targeted deep phenotypic evaluation, prognosis, and eligibility for emerging gene-specific therapies.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and Expression Analysis of the Formin Gene Family in <i>Neopyropia yezoensis</i> Under Different Environmental Conditions.","authors":"Shengqi Ye, Hongxin Ji, Lianxuan Chen, Jingwen Qi, Haihong Chen","doi":"10.3390/genes17091089","DOIUrl":"10.3390/genes17091089","url":null,"abstract":"<p><p><b>Background/Objectives:</b><i>Neopyropia yezoensis</i> is an economically important intertidal red alga that frequently experiences fluctuations in temperature, light intensity, and water availability. Formins are key regulators of actin nucleation and cytoskeletal dynamics, but their functions and stress-responsive roles in red algae remain poorly understood. This study aimed to systematically identify and characterize the Formin gene family in <i>N. yezoensis</i> and investigate their expression responses to different environmental stresses. <b>Methods:</b> Formin family members were identified from the <i>N. yezoensis</i> genome using HMMER and BLAST (2.17.0) searches based on the conserved FH2 domain, followed by domain validation. Gene structures, conserved motifs, physicochemical properties, predicted subcellular localization, protein structures, chromosomal distribution, phylogenetic relationships, and cis-acting elements in the upstream regions were analyzed. The expression patterns of the identified Formin genes were further examined by qRT-PCR under different temperature (4, 10, and 24 °C), light intensity (20, 60, and 100 μmol photons m^-2 s^-1), and desiccation/rehydration conditions. <b>Results:</b> Three Formin genes, designated NpyFormin01-03, were identified in <i>N. yezoensis</i>. All three encoded proteins contained the conserved FH2 domain but differed in motif composition, domain architecture, predicted subcellular localization, and structural features. NpyFormin01 contained additional PTEN_C2 and PTP_DSP_cys domains, whereas NpyFormin02 and NpyFormin03 contained only the FH2 domain. Phylogenetic analysis showed that the <i>N. yezoensis</i> Formins clustered with Formins from other red algae. Promoter analysis identified multiple predicted cis-acting elements associated with light, temperature, environmental, and phytohormone responses. Expression analysis revealed distinct responses among the three genes under the tested environmental conditions. Notably, NpyFormin01 was significantly upregulated under high-temperature treatment (24 °C), whereas NpyFormin02 and NpyFormin03 showed no statistically significant expression changes under the tested conditions. <b>Conclusions:</b> This study provides a systematic characterization of the Formin gene family in <i>N. yezoensis</i>. The differences in protein architecture, structural features, promoter cis-acting elements, and environmental-responsive expression patterns suggest potential functional divergence among NpyFormins. In particular, NpyFormin01 represents a potential heat-responsive candidate gene and may contribute to cytoskeletal regulation during environmental stress adaptation in <i>N. yezoensis</i>. These findings provide a basis for further investigation of the molecular functions of Formins in red algae.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Omics-Based Sperm-Retrieval Prediction in Non-Obstructive Azoospermia: A Critical Narrative Review and Validation Framework.","authors":"Aris Kaltsas, Maria-Anna Kyrgiafini, Eleftheria Markou, Michael Chrisofos","doi":"10.3390/genes17091088","DOIUrl":"10.3390/genes17091088","url":null,"abstract":"<p><p>In non-obstructive azoospermia (NOA), microdissection testicular sperm extraction can provide sperm for intracytoplasmic sperm injection, but retrieval fails in approximately half of procedures. Genomic, transcriptomic, noncoding RNA, proteomic, metabolomic, and microbiome studies have reported molecular associations and prediction estimates. This critical narrative review examines the requirements for an assay-model system to support preoperative retrieval counseling. A focused PubMed/MEDLINE search updated on 31 August 2026 and targeted reference checking identified representative human reports and methodological guidance. Selected reports mainly illustrate discovery, development, and same-source evaluation. Common limitations include small cohorts, local assay optimization, heterogeneous outcomes, incomplete calibration, and uncertain transportability. Established karyotyping and Y-chromosome testing must be distinguished from discovery-scale genomics, which currently supports etiologic and qualified genotype-specific counseling rather than a universal calibrated retrieval model. A routine-variable multicenter model reported an external-cohort area under the receiver-operating-characteristic curve (AUC) of 0.8301, although cohort provenance, calibration, and clinical utility require independent confirmation. An author-developed seven-gate framework integrates clinical-question definition, assay specification, model development, internal validation, external evaluation, incremental value, and prospective impact. Future omics studies should test incremental value beyond a prespecified routine-variable model in the same patients and assess calibration, threshold consequences, net benefit, assay failure, cost, and patient outcomes.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}