Genes & genomics最新文献

{"title":"Gene expression profile in ulcerative colitis patients: FOXO4, ALDOB, SLC26A3, SOD2 genes as potential biomarkers.","authors":"Yakup Ülger, Anıl Delik","doi":"10.1007/s13258-025-01625-y","DOIUrl":"https://doi.org/10.1007/s13258-025-01625-y","url":null,"abstract":"<p><strong>Background: </strong>Ulcerative colitis (UC) is a complex, chronic inflammatory disease that primarily impacts the colon mucosa. One of the key pathological contributors to the development and progression of inflammatory bowel disease (IBD) is oxidative stress, which results in reactive oxygen species (ROS)-induced mucosal damage. This stress leads to dysfunction of the intestinal barrier.</p><p><strong>Objectives: </strong>The purpose of this study is to examine the expression levels of genes involved in various inflammatory pathways, including autophagy, unfolded protein response (UPR), ubiquitination, metabolic pathways, and immune responses in the colon mucosa of patients with UC.</p><p><strong>Material and methods: </strong>Patients diagnosed with UC at Çukurova University, Balcalı Hospital, Gastroenterology Department between December 2023 and January 2024 were included in this prospective study. A total of 40 participants were included in the study: 27 ulcerative colitis patients and 13 controls. To isolate high-quality RNA, colon biopsy material obtained during colonoscopy was immediately placed in stabilization solution and stored at - 80 degrees Celsius. The relative quantification of target gene mRNA was determined using a Light Cycler. Subsequently, differences in gene expression between patients and the control group were evaluated using the Mann-Whitney U and Kruskal-Wallis tests.</p><p><strong>Results: </strong>In our study, FOXO4 gene expression increased in UC patients during both active and remission phases compared to the control group. The high expression of this gene is associated with its role in inflammation and cell death processes. Additionally, the high expression of ALDOB and SLC26A genes is linked to increased inflammation and energy demand. Lastly, the elevated expression of the SOD2 gene can be considered a response to oxidative stress-related inflammatory processes in the disease.</p><p><strong>Conclusion: </strong>These findings propose that these genes could serve as potential biomarkers for genomic identification and understanding the pathogenesis of UC.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular cloning, expression analysis, and functional characterization of Intelectin-1 from Chinese giant salamanders (Andrias davidianus).","authors":"Haolin Mo, Kexin Liu, Xiaoran An, Yongqing Chen, Jiajia Yu, Huixia Yu, Mingxing Yao, Weijia Song, Yang Li, Lixin Wang","doi":"10.1007/s13258-025-01630-1","DOIUrl":"https://doi.org/10.1007/s13258-025-01630-1","url":null,"abstract":"<p><strong>Background: </strong>Intelectin (ITLN) plays a pivotal role in innate immunity, inflammatory responses, and tumor progression. However, its physiological roles in caudate amphibians, such as Andrias davidianus, remain elusive.</p><p><strong>Objective: </strong>A proto-type of intelectin (AdITLN1) from A. davidianus was characterized, following which an AdITLN1 homology model was generated to analyze its expression profiles and functional characterizations.</p><p><strong>Methods: </strong>The intelectin1 gene (AdITLN1) was cloned, and its evolutionary relationship with ITLN1 from other species was explored. Additionally, a homology model was generated using Molecular Operating Environment (MOE) software, and the active binding pocket of AdITLN1 was identified. Infections with Aeromonas hydrophila were conducted to analyze changes in ITLN1 transcript levels in liver tissue. Finally, recombinant A. davidianus ITLN1 protein (rAdITLN1) was synthesized using prokaryotic expression, and its bacterial agglutination activity and impact on macrophage phagocytosis were examined.</p><p><strong>Results: </strong>Multiple sequence alignment and phylogenetic analysis indicated that AdITLN1 shared the closest evolutionary relationship with amphibians, with its structure being similar to that of human intelectin1 and Xenopus Embryonic Epidermal Lectin. Moreover, AdITLN1 mRNA was expressed in a wide range of tissues and was significantly up-regulated post-A. hydrophila infection. Meanwhile, the AdITLN1 protein was successfully expressed and purified in Escherichia coli (E. coli) BL21 (DE3). The recombinant AdITLN1 (rAdITLN1) displayed strong agglutination activity against different Gram-negative and Gram-positive bacteria. Lastly, The phagocytosis of rAdITLN1-treated E. coli by macrophages was significantly enhanced.</p><p><strong>Conclusion: </strong>The results of the present study demonstrated that AdITLN1 was a multifunctional immune protein with potent immunomodulatory activity. This study offers valuable insights into disease control in giant salamanders and the conservation of natural resources.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide analysis of TCP family genes and their constitutive expression pattern analysis in the melon (Cucumis melo).","authors":"Md Jahid Hasan Jone, Md Nure Adil Siddique, Manosh Kumar Biswas, Mohammad Rashed Hossain","doi":"10.1007/s13258-025-01617-y","DOIUrl":"10.1007/s13258-025-01617-y","url":null,"abstract":"<p><strong>Background: </strong>TCP proteins are plant-specific transcription factors that play essential roles in various developmental processes, including leaf morphogenesis and senescence, flowering, lateral branching, hormone crosstalk, and stress responses. However, a comprehensive analysis of genome-wide TCP genes and their expression patterns in melon is yet to be done.</p><p><strong>Objective: </strong>The present study aims to identify and analyze the TCP genes in the melon genome and understand their putative functions.</p><p><strong>Methods: </strong>The chromosomal location, gene structure, conserved motifs, protein domains, structural homology, cis-regulating elements, transcript expression patterns, and potential protein-protein interactions were analyzed using various databases and webtools.</p><p><strong>Results: </strong>A total of 29 putative TCP genes are identified in melon. These genes were classified into two classes: Class-I (13 genes) and Class-II (16 genes). The results revealed that the putative CmTCP genes are distributed across nine of the twelve melon chromosomes and exhibit diverse expression patterns in different tissues which mostly indicates their potential role in floral organ development, lateral branching, growth and development. Phylogenetic analysis suggests that some CmTCP genes may have similar functions to their homologs in other plant species, while others may have undergone functional diversification.</p><p><strong>Conclusion: </strong>This study paves the way for future investigations into the specific roles of individual CmTCP genes in melon and for elucidating the mechanisms by which TCP proteins regulate leaf elongation, floral development, and lateral branching.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"367-382"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CKAP4 is a potential therapeutic target to overcome resistance to EGFR-TKIs in lung adenocarcinoma.","authors":"Seongeun Song, Sangmyung Rhee","doi":"10.1007/s13258-024-01606-7","DOIUrl":"10.1007/s13258-024-01606-7","url":null,"abstract":"<p><strong>Background: </strong>Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are standard treatments for non-small cell lung cancer (NSCLC) patients with EGFR mutations; however, drug resistance limits their efficacy. Cytoskeleton-associated protein 4 (CKAP4) has been linked to cancer progression, but its role in EGFR-TKI resistance remains unclear.</p><p><strong>Objective: </strong>This study investigates the clinical relevance of CKAP4 as a therapeutic target to overcome EGFR-TKI resistance in lung adenocarcinoma (LUAD) patients.</p><p><strong>Methods: </strong>GEO datasets were analyzed to identify 24 differentially expressed genes associated with EGFR-TKI resistance, with CKAP4 selected via functional annotation and scoring using the VarElect tool. The prognostic significance of CKAP4 was evaluated using public databases, and its upregulation was confirmed in osimertinib-tolerant H1975 cells through quantitative reverse transcription-polymerase chain reaction.</p><p><strong>Results: </strong>Integrated bioinformatics analysis identified CKAP4 as strongly associated with EGFR-TKI resistance. Elevated CKAP4 expression was particularly linked to poorer clinical outcomes in LUAD patients. Notably, osimertinib-tolerant cells exhibited high CKAP4 expression, correlating positively with increased half-maximal inhibitory concentrations of EGFR-TKIs. LUAD patients with upregulated CKAP4 showed significantly reduced overall and relapse-free survival.</p><p><strong>Conclusion: </strong>This study underscores the prognostic value of CKAP4 in EGFR-mutated LUAD and highlights its potential as a therapeutic target to counter EGFR-TKI resistance.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"331-340"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptome analysis of wild soybean (Glycine soja) under salt stress and identification of salt-responsive genes.","authors":"Man Bo Lee, Taekyeom Kim, Dae Yeon Kim, Su Kyoung Lee, Jae Yoon Kim","doi":"10.1007/s13258-024-01599-3","DOIUrl":"10.1007/s13258-024-01599-3","url":null,"abstract":"<p><strong>Background: </strong>Soil salinity has been a serious threat to agricultural production worldwide, including soybeans. Glycine soja, the wild ancestor of cultivated soybeans, harbors high genetic diversity and possesses attractive rare alleles.</p><p><strong>Objective: </strong>We conducted a transcriptome analysis of G. soja subjected to salt stress to profile the transcriptomes and identify salt-responsive genes.</p><p><strong>Methods: </strong>G. soja was subjected to salt stress at 0, 24, and 48 h. RNA was sequenced using the Illumina NovaSeq 6000 platform. Transcriptome sequencing was used to identify differentially expressed genes (DEGs) and differential alternative splicing genes (DASGs) and to analyze alterations in salt-responsive genes.</p><p><strong>Results: </strong>A total of 249 and 1890 DEGs were identified at 24 and 48 h under salt stress, respectively. Among the DEGs, 45 and 252 transcription factors, including bHLH, MYB, and WRKY, were identified at 24 and 48 h, respectively. Additionally, 602 and 1850 DASGs were identified at 24 and 48 h, respectively. For DASGs, significant GO term enrichments included 'mRNA processing', 'Chromatin organization', 'Nucleus', and 'Transcription cofactor activity' at 48 h. The KEGG pathways, 'Spliceosome' and the 'mRNA surveillance pathway', were significantly enriched in DASGs at 48 h. Salt-responsive genes were identified in DEGs and/or DASGs, specifically GsJ3, GsACA12, GsACA13, GsHSFA2-like, and GsHSF30-like.</p><p><strong>Conclusion: </strong>Through the analysis of DEGs, DASGs, and transcription factor predictions, we identified key factors involved in the salt stress response and tolerance of G. soja, which could contribute to salt-tolerant soybean cultivar through genetic engineering strategies.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"351-365"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of SNPs associated with fatty acid contents in mutant soybean lines by a genome-wide association study.","authors":"Jeong Woo Lee, Jung Min Kim, Dae June Kim, Ji Su Seo, Bo-Keun Ha, Soon-Jae Kwon","doi":"10.1007/s13258-024-01608-5","DOIUrl":"10.1007/s13258-024-01608-5","url":null,"abstract":"<p><strong>Background: </strong>Vegetable oils are primarily composed of unsaturated fatty acids. Soybean [Glycine max (L.) Merr.] oil, accounting for 28% of the global production of vegetable oil, contains mainly two saturated fatty acids (palmitic acid and stearic acid) and three unsaturated fatty acids (oleic acid, linoleic acid, and linolenic acid) in seeds.</p><p><strong>Objective: </strong>The five fatty acids determine soybean oil quality. We aimed to identify genetic relationship between genomics and fatty acid contents in soybean mutant pool.</p><p><strong>Methods: </strong>This study used a mutant diversity pool (MDP) comprising 192 soybean lines. A genome-wide association study (GWAS) was conducted with the diverse fatty acid contents in MDP and 17,631 filtered SNPs from genotyping-by-sequencing (GBS).</p><p><strong>Results: </strong>The GWAS revealed nine significant SNPs within intragenic regions that were associated with fatty acid composition. These SNPs corresponded to six genes (Glyma.03g042500, Glyma.07g069200, Glyma.13g150200, Glyma.14g223100, Glyma.15g084700, and Glyma.15g274000), of which three (Glyma.03g042500, Glyma.13g150200, and Glyma.15g274000) were predicted to be candidate genes influencing oleic acid, linoleic acid, and linolenic acid contents. Analyses of SNP allelic effects revealed the largest and smallest significant differences in fatty acid contents were 5.53% (linolenic acid) and 0.4% (stearic acid), respectively.</p><p><strong>Conclusion: </strong>The present study detected significant phenotypic variations and genetic associations underlying the fatty acid composition of soybean seeds in MDP lines. The mutant seeds differed from the original cultivars in terms of fatty acids composition, with the allelic effects of significant SNPs influencing the fatty acid content in seeds. These findings may be useful for enhancing breeding strategies to optimize soybean oil quality for various uses.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"307-320"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative bioinformatics approaches reveal key hub genes in cyanobacteria: insights from Synechocystis sp. PCC 6803 and Geminocystis sp. NIES-3708 under abiotic stress conditions.","authors":"Abbas Karimi-Fard, Abbas Saidi, Masoud Tohidfar, Seyede N Emami","doi":"10.1007/s13258-025-01615-0","DOIUrl":"10.1007/s13258-025-01615-0","url":null,"abstract":"<p><strong>Background: </strong>Cyanobacteria, particularly Synechocystis sp. PCC 6803, serve as model organisms for studying acclimation strategies that enable adaptation to various environmental stresses. Understanding the molecular mechanisms underlying these adaptations provides insight into how cells adjust gene expression in response to challenging conditions.</p><p><strong>Objective: </strong>To analyze the transcriptome data of Synechocystis sp. PCC 6803 under light, salinity, and iron stress conditions and to identify hub genes potentially involved in stress response, specifically comparing the findings with Geminocystis sp. NIES-3708.</p><p><strong>Methods: </strong>A comprehensive bioinformatics approach was applied, integrating meta-analysis, weighted gene co-expression network analysis (WGCNA), and a Random Forest (RF) machine learning algorithm. These approaches underscore the robustness of our findings, allowing for a more nuanced understanding of gene interactions and their functional relevance in stress responses. This methodology was used to identify key hub genes in Synechocystis sp. PCC 6803 that may have conserved roles in Geminocystis sp. NIES-3708. A total of four potential hub genes, including slr1392, slr1484, sll1549, and sll1863, were identified. Among these, only sll1549 had a homolog (GM3708_2556) with 71% sequence similarity and 70% query coverage in Geminocystis sp. NIES-3708. The expression of GM3708_2556 was further evaluated under nitrate, salt, and combined salinity-nitrate stress conditions using RT-qPCR.</p><p><strong>Results: </strong>Transcript levels of GM3708_2556 increased significantly under salt stress (3.35-fold, p-value < 0.05) and combined salinity-nitrate stress (2.24-fold, p-value < 0.05) compared to control conditions, while no significant change was observed under nitrate stress alone. These results suggest that GM3708_2556 may play a crucial role in the organism's response to salt stress, with potential interactions in nitrate metabolism.</p><p><strong>Conclusion: </strong>This study highlights the gene GM3708_2556 as a significant factor in salt stress response, with implications for conserved functional roles across cyanobacterial species. Furthermore, the findings have potential relevance to biotechnology, particularly in engineering stress-resistant cyanobacterial strains for applications in sustainable agriculture and bioenergy production.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"383-397"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual-specificity phosphatase 23 functions as a promising prognostic biomarker in non-small cell lung cancer.","authors":"Seula Keum, Yoon Ji Lee, Jung-Woong Kim, Sangmyung Rhee","doi":"10.1007/s13258-024-01604-9","DOIUrl":"10.1007/s13258-024-01604-9","url":null,"abstract":"<p><strong>Background: </strong>The mechanical remodeling of tumor microenvironment is critical for non-small cell lung cancer (NSCLC) progression. Dual-specificity phosphatase 23 (DUSP23) has been previously identified as a mechano-responsive gene, but its role in NSCLC progression remains unknown.</p><p><strong>Objective: </strong>We aim to elucidate the clinical significance of DUSP23 in NSCLC progression.</p><p><strong>Methods: </strong>We analyzed the expression of DUSP23 in cancer using polyacrylamide hydrogels designed to mimic the stiffness of normal (soft; ~0.5 kPa) and cancerous (stiff; ~40 kPa) tissues. The prognostic significance of DUSP23 expression in patients was examined using public databases. Additionally, we conducted various cell-based assays and transcriptomic analyses in DUSP23-silenced NSCLC cell lines. A risk score prognosis model was constructed using univariate Cox regression and Kaplan-Meier analysis.</p><p><strong>Results: </strong>Our findings show that DUSP23 is upregulated in stiff matrices and is highly associated with poor prognosis in patients with solid cancers such as NSCLC and breast cancer. Silencing of DUSP23 resulted in decreased cell proliferation and invasion. Transcriptomic profiling revealed that 182 genes were downregulated, and 230 genes upregulated following DUSP23-depletion. Notably, 182 downregulated genes were enriched in cancer-related pathways, including cell cycle progression and cytoskeleton organization. Through KEGG pathway analysis, we identified 11 cancer-related genes and developed a prognostic risk model. In this model, the high-risk group of NSCLC patients exhibited significantly shorter overall survival compared to low-risk group, based on public datasets.</p><p><strong>Conclusion: </strong>Our study demonstrates the clinical significance of DUSP23 as a prognostic marker in NSCLC and highlights its potential role of DUSP23 in promoting NSCLC progression.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"321-329"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of novel CDH23 heterozygous variants causing autosomal recessive nonsyndromic hearing loss.","authors":"Baoqiong Liao, Wuming Xie, Rutian Liu, Qi Zhang, Ting Xie, Dan Jia, Shuwen He, Hailong Huang","doi":"10.1007/s13258-024-01611-w","DOIUrl":"10.1007/s13258-024-01611-w","url":null,"abstract":"<p><strong>Background: </strong>Hearing loss adversely impacts language development, acquisition, and the social and cognitive maturation of affected children. The hearing loss etiology mainly includes genetic factors and environmental factors, of which the former account for about 50-60%.</p><p><strong>Objective: </strong>This study aimed to investigate the genetic basis of autosomal recessive non-syndromic hearing loss (NSHL) by identifying and characterizing novel variants in the CDH23 gene. Furthermore, it seeks to determine the pathogenic potential of the noncanonical splice site variant c.2398-6G > A.</p><p><strong>Methods: </strong>Comprehensive clinical evaluation and whole-exome sequencing (WES) were performed on the girl. The WES analysis revealed two novel variants in the CDH23 gene, associated with nonsyndromic deafness 12 (DFNB12). To further explore the pathogenicity of these variants, functional studies involving in vivo splicing analysis were performed on the novel noncanonical splice site variant, c.2398-6G > A, which was initially classified as a variant of uncertain significance (VUS).</p><p><strong>Results: </strong>Whole-exome sequencing of the patient identified two compound heterozygous variants in CDH23: c.2398-6G > A, a noncanonical splice site variant, and c.6068C > A (p. Ser2023Ter), a nonsense mutation. In vitro splicing assays demonstrated that c.2398-6G > A caused aberrant splicing, leading to a frameshift (p. Val800Alafs*6) and the production of a truncated protein, as confirmed by structural protein analysis. The study revealed novel mutations as likely pathogenic, linking both variants to autosomal recessive NSHL.</p><p><strong>Conclusions: </strong>Our analyses revealed novel compound heterozygous mutations in CDH23 associated with autosomal recessive NSHL, thereby expanding the mutational landscape of CDH23-related hearing loss and increasing knowledge about the CDH23 splice site variants.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"293-305"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 novel frameshift TBX4 variant in a family with ischio-coxo-podo-patellar syndrome and variable severity.","authors":"Giada Moresco, Ornella Rondinone, Alessia Mauri, Rita Gorgoglione, Daniela Maria Grazia Graziani, Michal Dziuback, Monica Rosa Miozzo, Silvia Maria Sirchia, Luca Pietrogrande, Angela Peron, Laura Fontana","doi":"10.1007/s13258-024-01589-5","DOIUrl":"10.1007/s13258-024-01589-5","url":null,"abstract":"<p><strong>Background: </strong>Congenital anomalies of the knee are a spectrum of rare disorders with wide clinical and genetic variability, which are mainly due to the complex processes underlying knee development. Despite progresses in understanding pathomechanisms and associated genes, many patients remain undiagnosed.</p><p><strong>Objective: </strong>To uncover the genetic bases of a congenital patellar dislocation affecting multiple family members with variable severity.</p><p><strong>Methods: </strong>We performed ES in the proband and his father, both showing bilateral patellar dislocation, his sister with a milder similar condition, and his unaffected mother. Sanger sequencing was then performed in the proband's brother and paternal aunt, both affected as well.</p><p><strong>Results: </strong>ES and Sanger sequencing identified the presence of the novel heterozygous frameshift mutation c.735delT in the TBX4 gene in all affected family members. TBX4 is associated with autosomal dominant ischio-coxo-podo-patellar syndrome with/without pulmonary arterial hypertension (ICPPS, #147891), reaching a diagnosis in the family. Intrafamilial clinical heterogeneity suggests that other factors might be involved, such as additional variants in TBX4 or in other modifier genes. Interestingly, we identified three additional variants in the TBX4 gene in the proband only, whose phenotype is more severe. Despite being classified as benign, one of these variants is predicted to disrupt a splicing protein binding site, and may therefore affect TBX4 alternative splicing, accounting for the more severe phenotype of the proband.</p><p><strong>Conclusion: </strong>We expand and further delineate the genotypic and phenotypic spectrum of ICPPS. Further studies are necessary to shed light on the potential effect of this variant and on the variable phenotypic expressivity of TBX4-related phenotypes.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"341-349"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}