Frontiers in Genetics最新文献

{"title":"Structural characteristics of mitochondrial genome of <i>Spirobo-lus walkeri</i> (Spirobolida: Spirobolidae), and phylogenetic analysis of Diplopoda.","authors":"Wenwen Zhang, Shengjun Zhao, Lingna Li, Yingzhu Li, Hongyi Liu, Peng Cui","doi":"10.3389/fgene.2025.1566634","DOIUrl":"https://doi.org/10.3389/fgene.2025.1566634","url":null,"abstract":"<p><p>The phylogeny of Diplopoda, a group of ancient arthropod and an important component of modern terrestrial ecosystems, remains unclear. Here, the complete mitogenome of <i>Spirobolus walkeri</i> was determined. The newly sequenced complete mitogenome was circular DNA molecules with sizes of 14,879 bp. The mitogenome was composed of 37 genes and one control region. Negative AT-skews and positive GC-skews were found in whole mitogenome. The gene <i>COX1</i> used CGA as the start codon, while the other PCGs utilized ATN (A, T, G) as the start codons; however, the sequence of the stop codon was variable. The Ser2 exhibited the highest usage bias. All tRNAs have typical cloverleaf structures, except <i>trnS-AGC</i> and <i>trnM</i>. Phylogenetic analysis showed that <i>S. walkeri</i> and <i>Spirobolus bungii</i> shared a close relationship and that they were also closely related with <i>Narceus annularus</i>. This study helps resolve taxonomic ambiguities among morphologically similar species and provides data to support the establishment of evolutionary benchmarks for millipedes, including gene rearrangements and variations in tRNA structure.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1566634"},"PeriodicalIF":2.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752297","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":"Exploring the oncogenic role and prognostic value of <i>CKS1B</i> in human lung adenocarcinoma and squamous cell carcinoma.","authors":"Md Solayman Hossain, Tariqul Islam Tusar, Nairita Ahsan Faruqui, Tanjim Ishraq Rahaman, Yasin Arafath Sharker, Shimran Saharia Santo, Abu Tayab Moin, Yusha Araf, Ibrahim Khalil Afif, Shoaib Saikat, Mohammad Jakir Hosen","doi":"10.3389/fgene.2025.1449466","DOIUrl":"https://doi.org/10.3389/fgene.2025.1449466","url":null,"abstract":"<p><strong>Introduction: </strong>Lung cancer (LC) is a highly aggressive malignancy and remains a leading cause of cancer-related mortality worldwide. Non-small cell lung cancer (NSCLC), which includes adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC), accounts for the majority of these deaths. Due to the lack of early clinical symptoms and late-stage diagnosis, there is an urgent need for precise and targeted therapeutic strategies. Cyclin-dependent kinase regulatory subunit 1B (<i>CKS1B</i>), a key regulator of the cell cycle, has been implicated in various human cancers. Emerging evidence suggests that its upregulation is associated with poor prognosis in NSCLC, highlighting its potential as a biomarker for early detection and targeted therapy.</p><p><strong>Methods: </strong>In this study, we conducted a comprehensive bioinformatics analysis to evaluate the role of <i>CKS1B</i> in LUAD and LUSC. Differential gene expression analysis, survival analysis, immune infiltration correlation, and pathway enrichment analysis were performed using publicly available transcriptomic datasets. Additionally, gene interaction networks were analyzed to assess the functional significance of <i>CKS1B</i> in lung cancer progression.</p><p><strong>Results: </strong>Our findings indicate a significant overexpression of <i>CKS1B</i> in LUAD and LUSC compared to normal lung tissues. Survival analysis demonstrated that higher <i>CKS1B</i> expression correlates with poor prognosis in NSCLC patients. Immune infiltration analysis revealed a potential role of <i>CKS1B</i> in modulating the tumor microenvironment, further supporting its relevance in lung cancer progression. Functional enrichment analysis highlighted its involvement in critical oncogenic pathways, including cell cycle regulation and immune modulation.</p><p><strong>Discussion: </strong>The results suggest that <i>CKS1B</i> serves as a potential biomarker for early detection and prognosis in NSCLC. Its association with immune response pathways underscores its possible role in immunotherapy. However, despite these promising findings, further in vivo and in vitro studies are necessary to validate <i>CKS1B</i>'s clinical applicability as a diagnostic and therapeutic target for lung cancer.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1449466"},"PeriodicalIF":2.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752292","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":"weIMPUTE: a user-friendly web-based genotype imputation platform.","authors":"Mingliang Li, Zhuo Li, Defu Liu, Qi Li, Xiaodong Hu, Jun Yu, Jian Lin, Chunguang Bi, Guanshi Ye, Helong Yu, You Tang","doi":"10.3389/fgene.2025.1532464","DOIUrl":"https://doi.org/10.3389/fgene.2025.1532464","url":null,"abstract":"<p><strong>Background: </strong>Genotype imputation is a critical preprocessing step in genome-wide association studies (GWAS), enhancing statistical power for detecting associated single nucleotide polymorphisms (SNPs) by increasing marker size.</p><p><strong>Results: </strong>In response to the needs of researchers seeking user-friendly graphical tools for imputation without requiring informatics or computer expertise, we have developed weIMPUTE, a web-based imputation graphical user interface (GUI). Unlike existing genotype imputation software, weIMPUTE supports multiple imputation software, including SHAPEIT, Eagle, Minimac4, Beagle, and IMPUTE2, while encompassing the entire workflow, from quality control to data format conversion. This comprehensive platform enables both novices and experienced users to readily perform imputation tasks. For reference genotype data owners, weIMPUTE can be installed on a server or workstation, facilitating web-based imputation services without data sharing.</p><p><strong>Conclusion: </strong>weIMPUTE represents a versatile imputation solution for researchers across various fields, offering the flexibility to create personalized imputation servers on different operating systems.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1532464"},"PeriodicalIF":2.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752303","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":"Case report: Novel homozygous <i>ACVRL1</i> missense variant in a family with hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension: findings suggest a hypomorphic allele.","authors":"Akash Mathavan, Akshay Mathavan, Urszula Krekora, Adityanarayan Rao, Marc S Zumberg, Jeb Justice, Pinar Bayrak-Toydemir, Jamie McDonald, Ali Ataya","doi":"10.3389/fgene.2025.1554624","DOIUrl":"https://doi.org/10.3389/fgene.2025.1554624","url":null,"abstract":"<p><p>Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder caused by pathogenic variants in genes within the transforming growth factor beta (TGF-β) signaling pathway, such as <i>ACVRL1</i>, leading to haploinsufficiency. Homozygous variants in HHT-related genes are exceptionally rare and have not been reported in <i>ACVRL1</i>-related HHT to date. We report the first known instance of a novel homozygous missense variant in the <i>ACVRL1</i> gene (c.576C>G; p.Phe192Leu) identified in two siblings from a family of seven, in which three heterozygotes were also present. Comprehensive clinical evaluations revealed striking phenotypic differences between the homozygous and heterozygous family members. Both homozygous individuals exhibited early-onset pulmonary arterial hypertension and diffuse pulmonary arteriovenous malformations. One of them also demonstrated childhood-onset gastrointestinal bleeding-a manifestation unprecedented in HHT that typically has a late-adulthood onset. In contrast, the heterozygotes displayed either mild or equivocal features of HHT, supporting the classification of this variant as a hypomorphic allele. The novel missense variant is located within the intracellular glycine-serine (GS) domain of the protein, suggesting potential impacts on receptor regulation and downstream signaling. Although these findings expand the phenotypic spectrum of <i>ACVRL1</i>-related HHT, they remain limited to clinical observations. Experimental studies, including functional and molecular assays, are therefore essential to confirm the pathogenic impacts of this variant, validate its classification as a hypomorphic allele, and elucidate its effects on BMP-TGF-β signaling.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1554624"},"PeriodicalIF":2.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752285","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":"Corrigendum: Case report and literature review: delayed diagnosis of ARCL1B due to a newly reported homozygous mutation c.464A>C p. (Tyr155Ser) in the EFEMP2 gene.","authors":"Lixue Ouyang, Fan Yang, Hongyu Duan, Chuan Wang","doi":"10.3389/fgene.2025.1589037","DOIUrl":"https://doi.org/10.3389/fgene.2025.1589037","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fgene.2024.1453195.].</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1589037"},"PeriodicalIF":2.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729732","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":"CLMT: graph contrastive learning model for microbe-drug associations prediction with transformer.","authors":"Liqi Xiao, Junlong Wu, Liu Fan, Lei Wang, Xianyou Zhu","doi":"10.3389/fgene.2025.1535279","DOIUrl":"10.3389/fgene.2025.1535279","url":null,"abstract":"<p><p>Accurate prediction of microbe-drug associations is essential for drug development and disease diagnosis. However, existing methods often struggle to capture complex nonlinear relationships, effectively model long-range dependencies, and distinguish subtle similarities between microbes and drugs. To address these challenges, this paper introduces a new model for microbe-drug association prediction, CLMT. The proposed model differs from previous approaches in three key ways. Firstly, unlike conventional GCN-based models, CLMT leverages a Graph Transformer network with an attention mechanism to model high-order dependencies in the microbe-drug interaction graph, enhancing its ability to capture long-range associations. Then, we introduce graph contrastive learning, generating multiple augmented views through node perturbation and edge dropout. By optimizing a contrastive loss, CLMT distinguishes subtle structural variations, making the learned embeddings more robust and generalizable. By integrating multi-view contrastive learning and Transformer-based encoding, CLMT effectively mitigates data sparsity issues, significantly outperforming existing methods. Experimental results on three publicly available datasets demonstrate that CLMT achieves state-of-the-art performance, particularly in handling sparse data and nonlinear microbe-drug interactions, confirming its effectiveness for real-world biomedical applications. On the MDAD, aBiofilm, and Drug Virus datasets, CLMT outperforms the previously best model in terms of Accuracy by 4.3%, 3.5%, and 2.8%, respectively.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1535279"},"PeriodicalIF":2.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11936976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718589","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":"A rare variation of ERCC8 gene cause Cockayne syndrome in a Chinese family.","authors":"Fengjuan Ding, Fei Hou, Bowen Zhao, Hua Jin","doi":"10.3389/fgene.2025.1531832","DOIUrl":"10.3389/fgene.2025.1531832","url":null,"abstract":"<p><strong>Background: </strong>Cockayne syndrome (CS) is a multisystem degenerative disorder in which dysplasia and microcephaly represent the primary criteria for diagnosis. we present the cases of two patients who exhibited distinctive facial features and a range of other clinical manifestations, including growth failure, developmental delay, microcephaly, dental anomalies, and unstable gait.</p><p><strong>Methods: </strong>Clinical information pertaining to the patient's family was collated and the Pedigree chart was drawn. Two milliliters of peripheral blood were drawn from each of the two patients (III1and III3) and their parents, The causative genes were identified by Medical exome sequencing. Furthermore, the pregnant women underwent amniotic fluid prenatal diagnosis at mid-pregnancy (III5).</p><p><strong>Results: </strong>Medical exome sequencing revealed that both patients had a homozygous deletion of Exon4 in the ERCC8 gene and that both parents were carriers. Prenatal diagnosis by amniotic fluid confirmed that the fetus (III5) did not carry the variant.</p><p><strong>Conclusion: </strong>This clarified the diagnosis at the genetic level, deepened our understanding of the disease, and facilitated the ability to provide accurate genetic counseling and prenatal diagnosis, with the goal of reducing the number of new affected individuals in the family.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1531832"},"PeriodicalIF":2.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11936978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718587","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 validation of key biomarkers associated with immune and oxidative stress for preeclampsia by WGCNA and machine learning.","authors":"Tiantian Yu, Guiying Wang, Xia Xu, Jianying Yan","doi":"10.3389/fgene.2025.1500061","DOIUrl":"10.3389/fgene.2025.1500061","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Preeclampsia (PE), a major obstetric disorder marked by dysfunction in both placental and maternal vascular systems, continues to pose critical challenges in global maternal healthcare. This multisystem pregnancy complication contributes significantly to adverse perinatal outcomes and remains a leading cause of pregnancy-related morbidity worldwide. However, the available treatment options at present remain restricted. Our investigation employs an integrative bioinformatics approach to elucidate critical molecular signatures linked to the interplay between immunological dysregulation and oxidative stress mechanisms in PE pathogenesis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this study, we sourced the dataset from the GEO database with the aim of pinpointing differentially expressed genes (DEGs) between PE samples and control samples. Genes associated with oxidative stress were procured from the Genecards database. Next, we employed a comprehensive approach. This involved integrating WGCNA, GO and KEGG pathway analyses, constructing PPI networks, applying machine learning algorithms, performing gene GSEA, and conducting immune infiltration analysis to identify the key hub genes related to oxidative stress. Diagnostic potential of candidate biomarkers was quantitatively assessed through ROC curve modeling. Additionally, we constructed a miRNA - gene regulatory network for the identified diagnostic genes and predicted potential candidate drugs. In the final step, we validated the significant hub gene using independent external datasets, the hypoxia model of the HTR-8/SVneo cell line, and human placental tissue samples.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;At last, leptin (LEP) was identified as a core gene through screening and was found to be upregulated. The results of quantitative real-time polymerase chain reaction (qRT -PCR) and immunohistochemistry validation were consistent with those obtained from the datasets. KEGG analysis revealed that LEP was significantly enriched in \"allograft rejection,\" \"antigen processing,\" \"ECM receptor interaction\" and \"graft &lt;i&gt;versus&lt;/i&gt; host disease.\" GO analysis revealed that LEP was involved in biological processes such as \"antigen processing and presentation,\" \"peptide antigen assembly with MHC protein complex,\" \"complex of collagen trimers,\" \"MHC class II protein complex\" and \"mitochondrial protein containing complex.\" Moreover, immune cell analysis indicated that T follicular helper cells, plasmacytoid dendritic cells, neutrophils, and activated dendritic cells were positively correlated with LEP expression, whereas γδT cells, eosinophils, and central memory CD4&lt;sup&gt;+&lt;/sup&gt; T cells showed a negative correlation. These findings suggest that LEP influences the immune microenvironment of PE through its interaction with arious immune cells. In addition, 28 miRNAs and 15 drugs were predicted to target LEP. Finally, the overexpression of LEP was verified using independent external datasets,","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1500061"},"PeriodicalIF":2.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729733","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 determinism of cortisol levels in pig.","authors":"Elena Terenina, Nathalie Iannuccelli, Yvon Billon, Katia Fève, Laure Gress, Darya Bazovkina, Pierre Mormede, Catherine Larzul","doi":"10.3389/fgene.2025.1461385","DOIUrl":"10.3389/fgene.2025.1461385","url":null,"abstract":"<p><p>In facing the challenge of sustainability, animal breeding provides the option to improve animal robustness. In the search for new selection criteria related to robustness, the hypothalamic-pituitary-adrenocortical (HPA) axis is studied as a major neuroendocrine system involved in metabolic regulations and adaptive responses. Indeed, HPA axis activity is strongly influenced by genetic factors acting at several levels of the axis. The adrenocorticotropic hormone (ACTH) stimulation test has long been used to analyze interindividual and genetic differences in HPA axis activity in several species, including pigs. To uncover the genetic determinism of HPA activity and its influence on functional traits and robustness, a divergent selection experiment was carried out for three generations in a Large White pig population based on plasma cortisol levels measured one hour after injection of ACTH. In the present study the response to selection was very strong (confirming our previous studies), with a heritability value of cortisol level after ACTH injections reaching 0.64 (±0.03). The difference between the two divergent lines was around five genetic standard deviations after three selection steps. A genome-wide association study pointed out the importance of the glucocorticoid receptor gene (<i>NR3C1</i>) in this response. The measurement of plasma corticosteroid-binding globulin (CBG) binding capacity excluded any significant role of CBG in this selection process. The phenotypic effect of selection on body weight and growth rate was modest and/or inconsistent across generations. The HPA axis, a major neuroendocrine system involved in adaptation processes is highly heritable and responsive to genetic selection. The present experiment confirms the importance of glucocorticoid receptor polymorphism in genetic variation of HPA axis activity-in addition to the previously demonstrated role of CBG gene polymorphism. Further studies will explore the effect of this divergent selection on production and robustness.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1461385"},"PeriodicalIF":2.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11936974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718590","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":"Prenatal diagnosis of intellectual disability, autosomal dominant 29 with a nonsense pathogenic variant in <i>SETBP1</i>: a case report and literature review.","authors":"Zhuo Wei, Liying Yao, Lei Zhang, Shanshan Li, Meiyi Xu, Dan Wu, Wen Li, Ying Chang","doi":"10.3389/fgene.2025.1463485","DOIUrl":"10.3389/fgene.2025.1463485","url":null,"abstract":"<p><strong>Introduction: </strong>Intellectual disability, autosomal dominant 29 is a rare disorder resulting from pathogenic variants of <i>SETBP1</i> gene with no specific mutation hotspot identified. Systematic descriptions of new cases are crucial for understanding the genotypic and phenotypic spectrums of the disease.</p><p><strong>Case presentation: </strong>A pregnant woman was referred to the prenatal diagnosis center at our hospital because she has an intellectual disability and has previously given birth to a child with intellectual disabilities. Karyotype, CNV-seq and whole-exome sequencing (WES) were employed to investigate the potential genetic issues in the family. The <i>SETBP1</i> NM_015559.2: c.2425C>T (p.Gln809*) nonsense variant was found in the proband and mother, who were diagnosed with MRD29. Amniocentesis and genetic analysis (CNV-seq and sanger sequencing for mutation site) were performed as fetal cortical abnormalities and subependymal cystic area presented by ultrasonic examination at 25 + 5 gestational weeks. The genetic analysis confirmed the <i>SETBP1</i> c.2425C>T (p.Gln809*) nonsense mutation in the fetus. The parents terminated the pregnancy at 30 + 4 gestational weeks.</p><p><strong>Conclusion: </strong>The <i>SETBP1</i> NM_015559.2: c.2425C>T (p.Gln809*) nonsense variant is pathogenic and <i>SETBP1</i> haploinsufficiency may be associated with fatal cortical abnormalities. More prenatal clinical data is helpful for a better productive decision making and patient management.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1463485"},"PeriodicalIF":2.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11936921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718667","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}