Frontiers in Genetics最新文献

{"title":"Identification and functional characterization of <i>ABCA4</i> gene variants in three patients with Stargardt disease or retinitis pigmentosa.","authors":"Qi Luo, Juan Huang, Lu Shi, Guanghong Zhang, Linping Xue, Kehu Wu, Xiaoyu Li, Lei Yang, Dujun Li, Liangwei Mao, Jihong Luo","doi":"10.3389/fgene.2025.1516872","DOIUrl":"10.3389/fgene.2025.1516872","url":null,"abstract":"<p><strong>Introduction: </strong>The diversity of phenotypes, ranging from inherited retinal dystrophies (such as Stargardt disease 1, cone-rod dystrophy 3, and retinitis pigmentosa 19) to late-onset age-related macular degeneration 2, has been attributed to loss-of-function variants in the ABCA4 gene. In this study, we aimed to identify and analyze potential pathogenic ABCA4 variants in patients with Stargardt disease or retinitis pigmentosa and to explore the impact of an intronic variant (NM_000350.3:c.6386 + 4A>G) on mRNA splicing.</p><p><strong>Methods: </strong>We enrolled three patients from unrelated families with Stargardt disease or retinitis pigmentosa after comprehensive ophthalmological evaluations were performed. Whole-exome sequencing and Sanger sequencing were applied for mutation screening, focusing on inherited retinal dystrophy-related genes. Additionally, the splicing alteration caused by c.6386 + 4A>G was functionally characterized by a minigene splicing assay.</p><p><strong>Results: </strong>Five ABCA4 germline variants were detected in three patients: one frameshift, one nonsense, one splicing, and two missense variants. Furthermore, two pathogenic and two likely pathogenic variants and one variant of uncertain significance were determined according to ACMG/AMP and ClinGen sequence variant interpretation (SVI) guidelines. The minigene splicing assay result proved that c.6386 + 4A>G affected the wild-type donor splice-site recognition of intron 46 and yielded a truncated transcript with a 47-bp deletion in exon 46.</p><p><strong>Discussion: </strong>Our study identified two novel ABCA4 variants, expanding the mutational spectrum of the ABCA4 gene in Stargardt disease and retinitis pigmentosa while providing new insights into the molecular pathology of ABCA4 splicing defects.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1516872"},"PeriodicalIF":2.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553365","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":"Role of inflammation-related genes as prognostic biomarkers and mechanistic implications in idiopathic pulmonary fibrosis.","authors":"Bing Bai, Wenfei Zhao, Fazhan Li, Yang Mi, Pengyuan Zheng","doi":"10.3389/fgene.2025.1602588","DOIUrl":"10.3389/fgene.2025.1602588","url":null,"abstract":"<p><strong>Introduction: </strong>Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive lung disorder characterized by excessive fibrosis and structural remodeling of lung tissue. The role of inflammation in developing and progressing IPF is increasingly recognized as critical. However, the precise mechanisms and pathways of inflammation in IPF remain unclear. This study aimed to identify inflammation-related genes in IPF and develop a prognostic risk model using machine learning approaches.</p><p><strong>Methods: </strong>The IPF dataset GSE70866 from the Gene Expression Omnibus database was analyzed to identify inflammation-related genes. Unsupervised clustering algorithms were used to classify IPF samples, followed by weighted gene co-expression network analysis (WGCNA) to identify highly correlated genes. Least absolute shrinkage and selection operator (LASSO) regression was then applied, and the intersection of results pinpointed critical hub genes, primarily <i>CCL2</i> and <i>STAB1</i>. A rat model of pulmonary fibrosis was established, and lentivirus transfection was used to knock down <i>CCL2</i> expression. The transfection effect and hub gene expression were validated using Quantitative polymerase chain reaction, Western blot, immunohistochemistry, enzyme-linked immunosorbent assay, hematoxylin-eosin staining, and Masson's trichrome staining. Levels of α-SMA and COL1A1 were also assessed.</p><p><strong>Results: </strong>WGCNA and LASSO regression analyses identified <i>CCL2</i> and <i>STAB1</i> as significant contributors to IPF, closely associated with patient prognosis and immune cell infiltration. Protein-protein interaction network analysis established <i>CCL2</i> as a novel biomarker for IPF. In a rat model of IPF, <i>CCL2</i> expression was significantly elevated compared to that in the controls. Knockdown of <i>CCL2</i> expression alleviated pulmonary fibrosis and reduced the expression of COL1A1 protein and α-SMA protein. <i>CCL2</i> promotes the expression of COL1A1 protein and α-SMA proteins, suggesting that the mechanism of inflammation-induced pulmonary fibrosis may involve the regulation of COL1A1 and α-SMA by <i>CCL2</i>.</p><p><strong>Discussion: </strong>These findings establish <i>CCL2</i> as a promising biomarker and potential therapeutic target for IPF.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1602588"},"PeriodicalIF":2.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553370","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":"Application of non-invasive prenatal testing for fetal chromosomal disorders in low-risk pregnancies: a follow-up study in central China.","authors":"Qiuxiang Huang, Qiao Xu, Meihuan Chen, Wenli Fan, Hailong Huang","doi":"10.3389/fgene.2025.1574775","DOIUrl":"10.3389/fgene.2025.1574775","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the performance and screening value of noninvasive prenatal testing (NIPT) in low-risk pregnancies.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 60193 low-risk pregnancies over the last 5 years. Whole-genome sequencing of maternal plasma cell-free DNA was performed using next-generation sequencing. NIPT-positive results were confirmed using amniocentesis with karyotyping and/or copy number variation sequencing and chromosomal microarray analysis. Fetal outcomes were assessed using electronic medical records or telephone calls.</p><p><strong>Results: </strong>Overall, 598 (0.99%) NIPT-positive cases were identified. The distribution of chromosomal abnormalities included sex chromosome aneuploidies (SCAs; 55.85%), rare autosomal aneuploidies (RAAs; 20.40%), copy number variations (CNVs; 11.20%), trisomy 21 (T21; 6.86%), trisomy 13 (T13; 4.01%), and trisomy 18 (T18; 1.67%). A total of 572 (95.65%) patients with NIPT-positive results underwent amniocentesis, and 55.77% (319/572) cases were confirmed. The positive predictive values (PPV) for T21, T18, T13, SCAs, RAAs, and CNVs were 87.50%, 60.00%, 34.78%, 58.97%, 32.50%, and 69.70%, respectively, and the PPV for the trisomy was higher than that for the X-monomer in SCAs. NIPT-positive results for RAAs were common in T8, T10, T16 and T20, but T16 was the most common true positive result, accounting for 33.33% (13/39) of the cases. The termination rates of true-positive pregnancies were 100% (T21, T18 and T13), 79.49% (RAAs), 67.39% (CNVs) and 78.07% (SCAs).</p><p><strong>Conclusion: </strong>This study highlights the importance of genome-wide screening based on NIPT in low-risk pregnancies. Prenatal screening by NIPT has a high sensitivity and PPV. Moreover, it can greatly reduce invasive procedures and birth defects.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1574775"},"PeriodicalIF":2.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553347","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":"Whole genome sequencing and functional annotation of <i>Fusarium oxysporum</i> f. sp. <i>lentis</i> to unravel virulence and secondary metabolite biosynthesis gene clusters.","authors":"Sanjay Kharte, Ashish Kumar, Priyamvada Mishra, R S Ramakrishnan, Stuti Sharma, Nishi Mishra, Puneet Singh Chauhan, Radheshyam Sharma, Vedant Gautam, Shweta Tiwari, Vinod Goyal, Sonu Sharma, G K Koutu, N K Joshi","doi":"10.3389/fgene.2025.1585510","DOIUrl":"10.3389/fgene.2025.1585510","url":null,"abstract":"<p><strong>Background: </strong><i>Fusarium oxysporum</i> f. sp. <i>lentis</i> is a major fungal pathogen that causes vascular wilt in lentil crops, leading to significant reductions in yield. Despite its importance, the genetic underpinnings of this pathogen remain poorly understood.</p><p><strong>Methods: </strong>We performed whole-genome sequencing of <i>F. oxysporum</i> f. sp. <i>lentis</i> using the Illumina Shotgun Sequencing platform. The resulting high-quality genome assembly consisted of 12,366 contigs with a total length of 124.48 Mb. Genome completeness was evaluated using Benchmarking Universal Single-Copy Orthologs (BUSCO) analysis, and functional annotation was performed through comparisons with several public databases, including Uniprot, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Pfam, and Clusters of Orthologous Groups (COG). Pathogenicity-related genes were identified using the PHI-base database, and secondary metabolite biosynthesis was analyzed with AntiSMASH.</p><p><strong>Results: </strong>The genome assembly achieved 99% completeness, identifying 116,998 protein-coding genes. A total of 16,779 carbohydrate-active enzymes (CAZymes) could be detected, highlighting the pathogen's potential for plant cell wall degradation. Pathogenicity analysis revealed genes linked with moderate virulence. AntiSMASH detected 77 biosynthetic gene clusters (BGCs), including those encoding Type I polyketide synthases (T1PKS) and non-ribosomal peptide synthetases (NRPS), which may contribute to pathogenicity.</p><p><strong>Discussion: </strong>The comprehensive genomic analysis of <i>F. oxysporum</i> f. sp. <i>lentis</i> offers valuable insights into its pathogenic mechanisms, including plant cell wall degradation and secondary metabolite production. These findings pave the way for future research on host-pathogen interactions and the development of targeted disease management strategies.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1585510"},"PeriodicalIF":2.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553371","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":"Epigenetic study of the long-term effects of gulf War illness.","authors":"B C Jones, J P O'Callaghan, D G Ashbrook, L Lu, P Prins, W Zhao, K Mozhui","doi":"10.3389/fgene.2025.1553410","DOIUrl":"10.3389/fgene.2025.1553410","url":null,"abstract":"<p><strong>Introduction: </strong>Gulf War Illness is a chronic multisymptomatic disorder that affects as many as 25-35% of the military personnel who were sent to the Persian Gulf war in 1991. The illness has many debilitating symptoms, including cognitive problems, gastrointestinal symptoms, and musculoskeletal pain. Those so afflicted have been sick for more than 30 years and, therefore, it has become imperative to understand the etiology of Gulf War Illness and then produce treatments to ease the symptoms. We hypothesized that the length of the disease was reflected in epigenetic modification of possibly several genes related to the symptoms.</p><p><strong>Methods: </strong>We subjected male and female mice from 11 BXD strains to combined corticosterone and the sarin surrogate, diisopropylfluorophosphate, to emulate the physiological stress of war and the potential exposures to organophosphate pesticides and nerve agent in theater. Three hundred days after treatment, we used Methyl-CpG-binding domain sequencing (MBD-seq) to assay genome-wide methylation.</p><p><strong>Results: </strong>The analysis revealed 20 methylated genes, notably Eif2b5, that regulates myelin production.</p><p><strong>Discussion: </strong>Loss of myelin with accompanying musculoskeletal pain is a major symptom of Gulf War Illness. Our work demonstrates multiple genes were methylated by exposure to organophosphates and glucocorticoids. These genes point to biochemical mechanisms that may be targets for therapeutic intervention.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1553410"},"PeriodicalIF":2.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553354","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":"Regulation of term and preterm labor: genetics and epigenetics.","authors":"Kaiyi Sun, Ning Wang, Yuanyuan Liu, Lu Gao","doi":"10.3389/fgene.2025.1594030","DOIUrl":"10.3389/fgene.2025.1594030","url":null,"abstract":"","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1594030"},"PeriodicalIF":2.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553369","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":"Data simulation to optimize frameworks for genome-wide association studies in diverse populations.","authors":"Jacquiline W Mugo, Nicola Mulder, Emile R Chimusa","doi":"10.3389/fgene.2025.1559496","DOIUrl":"10.3389/fgene.2025.1559496","url":null,"abstract":"<p><p>Whole-genome or genome-wide association studies (GWAS) have become a fundamental part of modern genetic studies and methods for dissecting the genetic architecture of common traits based on common polymorphisms in random populations. It is hoped that there would be many potential uses of these identified variants, including a better understanding of the pathogenesis of traits, disease risk prediction, discovery of biomarkers, and clinical prediction of drug treatments for populations and global health. Questions have been raised about whether associations that are largely discovered in European ancestry populations are replicable in diverse populations, can inform medical decision-making globally, and how efficiently current GWAS tools perform in populations of high genetic diversity, multi-wave genetic admixture, and low linkage disequilibrium, such as African populations. Here, we discuss some of the challenges in association mapping and leverage genomic data simulation to mimic structured African, European, and multi-way admixed populations to evaluate the replicability of association signals from current state-of-the-art GWAS tools. We use the results to discuss optimized frameworks for the analysis of GWAS data in diverse populations. Finally, we outline the implications, challenges, and opportunities these studies present for populations of non-European descent.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1559496"},"PeriodicalIF":2.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553352","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":"Integrative bioinformatics analysis and experimental validation reveals key genes and regulatory mechanisms in the development of gout.","authors":"Ye Yuan, Zhiqiang Gao, Jianhong Chen, Yuejing Liu, Jingguo Zhou","doi":"10.3389/fgene.2025.1598835","DOIUrl":"10.3389/fgene.2025.1598835","url":null,"abstract":"<p><strong>Background and aims: </strong>Gout is a prevalent inflammatory arthropathy caused by monosodium urate crystal deposition, yet its molecular pathogenesis remains incompletely understood. This study aimed to identify key genes and elucidate regulatory mechanisms underlying gout development through bioinformatics analysis combined with experimental validation.</p><p><strong>Methods: </strong>Transcriptome dataset GSE160170 and single-cell dataset GSE211783 were analyzed using differential expression analysis and weighted gene co-expression network analysis (WGCNA). Functional enrichment, protein-protein interaction (PPI), ceRNA, and transcription factor networks were constructed. Immune cell infiltration was analyzed using CIBERSORTx. Molecular docking predicted therapeutic compounds. Experimental validation included qRT-PCR, Western blot, gene knockdown/overexpression, and functional assays.</p><p><strong>Results: </strong>Among 329 gout-related genes identified, CXCL8, PTGS2, and IL10 emerged as key regulators involved in cell-cell adhesion, leukocyte activation, and NF-κB signaling. Immune infiltration revealed significant upregulation of M2 macrophages, activated mast cells, activated NK cells, and γδ T cells in gout samples. CeRNA network identified KCNQ1OT1 and hsa-mir-98-5p as regulatory elements, while CEBPB, STAT3, RELA, and NFKB1 were key transcription factors. Molecular docking suggested pergolide as a therapeutic candidate. Single-cell analysis confirmed high expression of key genes in T/NK cells and myeloid cells. Western blot validation showed upregulated protein expression of key genes in the gout model. PTGS2 knockdown enhanced cell viability and reduced apoptosis, while overexpression promoted inflammatory cytokine production and NF-κB pathway activation.</p><p><strong>Conclusion: </strong>This study systematically elucidated the pivotal roles of CXCL8, PTGS2, and IL10 in gout pathogenesis, providing valuable molecular targets for therapeutic development.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1598835"},"PeriodicalIF":2.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553367","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 xyloglucan endotransglucosylase/hydrolase gene, <i>IbXTH16</i>, increases cold tolerance in transgenic sweetpotato.","authors":"Tao Yu, Jiaquan Pan, Sitong Liu, Zitong Yang, Zhenlei Liu","doi":"10.3389/fgene.2025.1629260","DOIUrl":"10.3389/fgene.2025.1629260","url":null,"abstract":"<p><strong>Introduction: </strong>Low temperature is a key environmental factor that threaten sweetpotato growth and development. In-depth studies on the gene functions underlying cold resistance are important for genetic engineering in sweetpotato.</p><p><strong>Methods: </strong>The <i>IbXTH16</i> gene was cloned using a homologous cloning approach. Its expression was detected in sweetpotato leaves subjected to low-temperature stress and brassinosteroid treatment. Subsequently, the <i>IbXTH16</i> gene was introduced into sweetpotato variety Lizixiang to generate <i>IbXTH16</i>-overexpressing plants, thereby enabling the functional validation of the <i>IbXTH16</i>.</p><p><strong>Results and discussion: </strong>The <i>IbXTH16</i> gene was cloned from the cold-tolerant variety LHS21. Its 879 bp coding sequence encoded a 292 aa protein with a molecular weight of 32.983 kDa and a pI of 8.47. The 2039 bp genomic sequence of <i>IbXTH16</i> contained two exons and one intron. The IbXTH16 protein was localized in the cell membrane. <i>IbXTH16</i> was strongly induced by 4°C and brassinosteroid. <i>IbXTH16</i> positively regulates cold tolerance of sweetpotato by activating the BR and proline pathways.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1629260"},"PeriodicalIF":2.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553346","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":"Clinical characteristics and genetic mutation analysis in 18 pediatric patients with Shwachman-Diamond syndrome.","authors":"Ruoying Wei, Kaihui Zhang, Chen Liu, Xuxia Wei, Qin Jiang, Ji-An Li, Meiling Huo, Yinggang Liu, Mohnad Abdalla, Li-An Du, Xiaomei Yang, Fu Li","doi":"10.3389/fgene.2025.1603782","DOIUrl":"10.3389/fgene.2025.1603782","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the clinical features and genetic mutation spectrum of 18 children with Shwachman-Diamond syndrome (SDS).</p><p><strong>Methods: </strong>Data from 18 children with SDS at Shandong University Affiliated Children's Hospital (Ji'nan Children's Hospital) between April 2016 and June 2024 were retrospectively analyzed. Variant sites were confirmed by Sanger sequencing in family lines.</p><p><strong>Results: </strong>Patients exhibited complex and diverse clinical symptoms, often involving multiple systems. The clinical features of this cohort included (1) early onset (median age: 1.5 months), diarrhea, trypsin reduction, neutropenia, and growth retardation and (2) high incidence of pancreatic imaging abnormalities, bone marrow hypoplasia, developmental malformations, and neurocognitive disorders. All patients had homozygous or compound heterozygous <i>SBDS</i> mutations, with 258+2T>C identified as the hotspot mutation (20/37), while 41A>T and 185A>C were newly discovered mutations.</p><p><strong>Conclusion: </strong>Patients with SDS exhibit clinical heterogeneity, and this study enriches the <i>SBDS</i> gene mutation spectrum. Genetic testing is valuable for early diagnosis.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1603782"},"PeriodicalIF":2.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553351","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}