Frontiers in Genetics最新文献

{"title":"Editorial: Pharmacogenetics of psychiatric disorders.","authors":"Sarah Allegra, Silvia De Francia, Stefano Comità, Maria Grazia Morgese, Thomas M Polasek","doi":"10.3389/fgene.2024.1523071","DOIUrl":"10.3389/fgene.2024.1523071","url":null,"abstract":"","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"15 ","pages":"1523071"},"PeriodicalIF":2.8,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028399","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":"DLBWE-Cys: a deep-learning-based tool for identifying cysteine S-carboxyethylation sites using binary-weight encoding.","authors":"Zhengtao Luo, Qingyong Wang, Yingchun Xia, Xiaolei Zhu, Shuai Yang, Zhaochun Xu, Lichuan Gu","doi":"10.3389/fgene.2024.1464976","DOIUrl":"10.3389/fgene.2024.1464976","url":null,"abstract":"<p><p>Cysteine S-carboxyethylation, a novel post-translational modification (PTM), plays a critical role in the pathogenesis of autoimmune diseases, particularly ankylosing spondylitis. Accurate identification of S-carboxyethylation modification sites is essential for elucidating their functional mechanisms. Unfortunately, there are currently no computational tools that can accurately predict these sites, posing a significant challenge to this area of research. In this study, we developed a new deep learning model, DLBWE-Cys, which integrates CNN, BiLSTM, Bahdanau attention mechanisms, and a fully connected neural network (FNN), using Binary-Weight encoding specifically designed for the accurate identification of cysteine S-carboxyethylation sites. Our experimental results show that our model architecture outperforms other machine learning and deep learning models in 5-fold cross-validation and independent testing. Feature comparison experiments confirmed the superiority of our proposed Binary-Weight encoding method over other encoding techniques. t-SNE visualization further validated the model's effective classification capabilities. Additionally, we confirmed the similarity between the distribution of positional weights in our Binary-Weight encoding and the allocation of weights in attentional mechanisms. Further experiments proved the effectiveness of our Binary-Weight encoding approach. Thus, this model paves the way for predicting cysteine S-carboxyethylation modification sites in protein sequences. The source code of DLBWE-Cys and experiments data are available at: https://github.com/ztLuo-bioinfo/DLBWE-Cys.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"15 ","pages":"1464976"},"PeriodicalIF":2.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022816","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":"Genotypic variability in stress responses of Sorghum bicolor under drought and salinity conditions.","authors":"Yahya Alzahrani, Abdulbaki Shehu Abdulbaki, Hameed Alsamadany","doi":"10.3389/fgene.2024.1502900","DOIUrl":"10.3389/fgene.2024.1502900","url":null,"abstract":"<p><strong>Introduction: </strong>Sorghum bicolor: widely cultivated in Asia and Africa, faces increasing challenges from climate change, specifically from abiotic stresses like drought and salinity. This study evaluates how different sorghum genotypes respond to separate and combined stresses of drought and salinity.</p><p><strong>Methods: </strong>Carried out with three replications using a randomized complete block design, the experiment measured biochemical and physiological parameters, including stomatal conductance, chlorophyll content, and antioxidant enzyme activities. Molecular analysis focused on stress-responsive gene expression.</p><p><strong>Results: </strong>Results indicated enhanced stress responses under combined conditions, with significant variation in antioxidant enzymatic activities among genotypes. Genotype-specific osmotic adjustments were observed through proline and glycine betaine accumulation. Physiological parameters such as chlorophyll content, cell membrane stability, stomatal conductance, and water potential were critical indicators of stress tolerance. Gene expression analysis revealed upregulation of stress-responsive genes, particularly under combined stress conditions.</p><p><strong>Discussion: </strong>Correlation and principal component analysis analyses highlighted the interdependencies among traits, emphasizing their roles in oxidative stress mitigation. Samsorg-17 exhibited the highest resilience due to consistently high levels of catalase, superoxide dismutase, and glycine betaine, alongside superior physiological attributes. CRS-01 showed moderate resilience with the highest Na/K ratio and notable photosynthesis rate and relative water content, but was less consistent in biochemical markers under stress. Samsorg-42 demonstrated resilience under specific conditions but was generally less robust than Samsorg-17 across most indicators. These findings emphasize the importance of developing stress-resilient sorghum cultivars through targeted breeding programs to enhance tolerance to drought and salinity in sustainable agriculture.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"15 ","pages":"1502900"},"PeriodicalIF":2.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023100","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 insights and therapeutic avenues: unraveling the role of polyunsaturated fatty acids as mediators between hypothyroidism and Von Willebrand disease through Mendelian randomization.","authors":"Wenting Zhou, Rui He, Ruwei Ou","doi":"10.3389/fgene.2024.1426401","DOIUrl":"10.3389/fgene.2024.1426401","url":null,"abstract":"<p><strong>Background: </strong>Previous observational studies have shown that Hypothyroidism is associated with Von Willebrand Disease (VWD), but the causal relationship has not been confirmed because of conflicting findings and confounding by mixing factors. There are also some studies suggesting that polyunsaturated fatty acids (PUFA) may be one of the potential mediators. In this study, we used a Mendelian randomization study to analyze the causal relationship between Hypothyroidism and VWD and to investigate whether polyunsaturated fatty acids mediate the effects of Hypothyroidism on VWD.</p><p><strong>Methods: </strong>Using a large publicly available genome-wide association study of predominantly European ancestry to obtain data on Hypothyroidism, VWD, and PUFA, we conducted a two-sample Mendelian randomization study to assess the causal relationship between Hypothyroidism and VWD and assess the potential role of Polyunsaturated fatty acids in mediating the causal pathway between Hypothyroidism and VWD. Finally, we also inferred reverse causality between VWD and Hypothyroidism. Inverse variance weighting (IVW) was the primary analytical method.</p><p><strong>Results: </strong>We found that Hypothyroidism may be negatively causally associated with the development of VWD and that PUFA have a role in mediating role in this process (the ratio of the mediating effect: 24.33%). The causal effects of Hypothyroidism and PUFA on VWD remained significant (p < 0.05) after correction of each other by MVMR.</p><p><strong>Conclusion: </strong>Our study unveils a novel negative correlation between hypothyroidism and VWD, further enriched by the discovery of partial mediation by PUFA. This groundbreaking finding not only advances our comprehension of VWD etiology but also opens promising avenues for its control and treatment. By elucidating the intricate interplay between hypothyroidism, PUFA, and VWD, our research pioneers a paradigm shift in therapeutic approaches, offering fresh perspectives for the management of this complex disorder.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"15 ","pages":"1426401"},"PeriodicalIF":2.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023131","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":"Detection of inversion with breakpoints in <i>ARSB</i> causing MPS VI by whole-genome sequencing: lessons learned and best practices.","authors":"Yufeng Huang, Wenyue Deng, Hui Huang, Xiankai Zhang, Xiaohong Chen, Jian Ye, Sukun Luo, Ting Yu, Hui Yao, Hao Du, Xuelian He","doi":"10.3389/fgene.2024.1452498","DOIUrl":"10.3389/fgene.2024.1452498","url":null,"abstract":"<p><strong>Introduction: </strong>Mucopolysaccharidosis type VI (MPSVI), an autosomal recessive lysosomal storage disorder caused by pathogenic variants in <i>ARSB</i> gene. Usually, whole exome sequencing (WES) can identify these variants, and if WES failed to detect causative variants, whole-genome sequencing (WGS) may be considered to investigate deep intronic variations and structural alterations in patients.</p><p><strong>Methods: </strong>Whole-exome sequencing (WES) and whole genome sequencing (WGS) were performed in a Chinese family having a boy with suspected diagnosis of MPS with macrocephaly, coarse facial features, broad forehead, thick lips, frontal bossing, craniosynostosis, blue spots, frequent upper respiratory infections, inguinal hernia, and dysostosis multiplex. Lysosomal enzymatic assays for leucocytes were used to assess the activity of arylsulfatase B of the boy's leucocytes. Sanger sequencing and karyotyping analysis were used to validate the variants identified in the boy and his parents.</p><p><strong>Results: </strong>This boy diagnosed with MPSVI based on clinical phenotypes and laboratory biochemical assays, and WES identified only a maternally inherited missense variant, c.908G>T (p.Gly303Val), in the <i>ARSB</i> gene. By performing WGS, we found a paracentric inversion involving chromosome 5q14.1q13.2 (78180730-138771424 inv), disrupting the <i>ARSB</i> gene on the proband and his father. The inversion was confirmed through karyotyping analysis, and the breakpoints were validated by agarose gel electrophoresis and Sanger sequencing.</p><p><strong>Disscussion: </strong>This study reminds us that WGS should be done when WES failed to achieve a molecular diagonosis, and it also underscores the importance of WGS especially in cases of high clinical suspicion.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"15 ","pages":"1452498"},"PeriodicalIF":2.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022441","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":"Understanding the impacts of drought on peanuts <i>(Arachis hypogaea</i> L.): exploring physio-genetic mechanisms to develop drought-resilient peanut cultivars.","authors":"Sameer Pokhrel, Prasanna Kharel, Swikriti Pandey, Stephanie Botton, Gema Takbir Nugraha, Corley Holbrook, Peggy Ozias-Akins","doi":"10.3389/fgene.2024.1492434","DOIUrl":"10.3389/fgene.2024.1492434","url":null,"abstract":"<p><p>Peanut is a vital source of protein, particularly in the tropical regions of Asian and African countries. About three-quarters of peanut production occurs worldwide in arid and semi-arid regions, making drought an important concern in peanut production. In the US about two-thirds of peanuts are grown in non-irrigated lands, where drought accounts for 50 million USD loss each year. The looming threat of climate change exacerbates this situation by increasing erratic rainfall. Drought not only reduces yield but also degrades product quality. Peanuts under drought stress exhibit higher levels of pre-harvest aflatoxin contamination, a toxic fungal metabolite detrimental to both humans and animals. One way to sustain peanut production in drought-prone regions and address pre-harvest aflatoxin contamination is by developing drought-tolerant peanut cultivars, a process that can be accelerated by understanding the underlying physiological and genetic mechanisms for tolerance to drought stress. Different physiological attributes and genetic regions have been identified in drought-tolerant cultivars that help them cope with drought stress. The advent of precise genetic studies, artificial intelligence, high-throughput phenotyping, bioinformatics, and data science have significantly improved drought studies in peanuts. Yet, breeding peanuts for drought tolerance is often a challenge as it is a complex trait significantly affected by environmental conditions. Besides technological advancements, the success of drought-tolerant cultivar development also relies on the identification of suitable germplasm and the conservation of peanut genetic variation.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"15 ","pages":"1492434"},"PeriodicalIF":2.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023062","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":"Integration of single-cell transcriptomics and bulk transcriptomics to explore prognostic and immunotherapeutic characteristics of nucleotide metabolism in lung adenocarcinoma.","authors":"Kai Zhang, Luyao Wang, Huili Chen, Lili Deng, Mengling Hu, Ziqiang Wang, Yiluo Xie, Chaoqun Lian, Xiaojing Wang, Jing Zhang","doi":"10.3389/fgene.2024.1466249","DOIUrl":"10.3389/fgene.2024.1466249","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) is a highly aggressive tumor with one of the highest morbidity and mortality rates in the world. Nucleotide metabolic processes are critical for cancer development, progression, and alteration of the tumor microenvironment. However, the effect of nucleotide metabolism on LUAD remains to be thoroughly investigated.</p><p><strong>Methods: </strong>Transcriptomic and clinical data of LUAD were downloaded and organized from TCGA and GEO databases. Genes related to nucleotide metabolism were downloaded from the Msigdb database. Genes associated with LUAD prognosis were identified using univariate COX analysis, and a prognostic risk model was constructed using the machine learning combination of Lasso + Stepcox. The model's predictive validity was evaluated using KM survival and timeROC curves. Based on the prognostic model, LUAD patients were classified into different nucleotide metabolism subtypes, and the differences between patients of different subtypes were explored in terms of genomic mutations, functional enrichment, tumor immune characteristics, and immunotherapy responses. Finally, the key gene SNRPA was screened, and a series of <i>in vitro</i> experiments were performed on LUAD cell lines to explore the role of SNRPA in LUAD.</p><p><strong>Result: </strong>LUAD patients could be accurately categorized into subtypes based on the nucleotide metabolism-related prognostic risk score (NMBRS). There were significant differences in prognosis between patients of different subtypes, and the NMBRS showed high accuracy in predicting the prognosis of LUAD patients. In addition, patients of different subtypes showed significant differences in genomic mutation and functional enrichment and exhibited different anti-tumor immune profiles. Importantly, NMBRS can be used to predict the responsiveness of LUAD patients to immunotherapy. The results of <i>in vitro</i> cellular experiments indicate that SNRPA plays an important role in the development and progression of lung adenocarcinoma.</p><p><strong>Conclusion: </strong>This study comprehensively reveals the prognostic value and clinical application of nucleotide metabolism in LUAD. A prognostic signature constructed based on genes related to nucleotide metabolism accurately predicted the prognosis of LUAD patients, and this signature can be used as a guide for LUAD immunotherapy.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"15 ","pages":"1466249"},"PeriodicalIF":2.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023102","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":"Co-methylation networks associated with cognition and structural brain development during adolescence.","authors":"Dawn Jensen, Jiayu Chen, Jessica A Turner, Julia M Stephen, Yu-Ping Wang, Tony W Wilson, Vince D Calhoun, Jingyu Liu","doi":"10.3389/fgene.2024.1451150","DOIUrl":"10.3389/fgene.2024.1451150","url":null,"abstract":"<p><strong>Introduction: </strong>Typical adolescent neurodevelopment is marked by decreases in grey matter (GM) volume, increases in myelination, measured by fractional anisotropy (FA), and improvement in cognitive performance.</p><p><strong>Methods: </strong>To understand how epigenetic changes, methylation (DNAm) in particular, may be involved during this phase of development, we studied cognitive assessments, DNAm from saliva, and neuroimaging data from a longitudinal cohort of normally developing adolescents, aged nine to fourteen. We extracted networks of methylation with patterns of correlated change using a weighted gene correlation network analysis (WCGNA). Modules from these analyses, consisting of co-methylation networks, were then used in multivariate analyses with GM, FA, and cognitive measures to assess the nature of their relationships with cognitive improvement and brain development in adolescence.</p><p><strong>Results: </strong>This longitudinal exploration of co-methylated networks revealed an increase in correlated epigenetic changes as subjects progressed into adolescence. Co-methylation networks enriched for pathways involved in neuronal systems, potassium channels, neurexins and neuroligins were both conserved across time as well as associated with maturation patterns in GM, FA, and cognition.</p><p><strong>Discussion: </strong>Our research shows that correlated changes in the DNAm of genes in neuronal processes involved in adolescent brain development that were both conserved across time and related to typical cognitive and brain maturation, revealing possible epigenetic mechanisms driving this stage of development.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"15 ","pages":"1451150"},"PeriodicalIF":2.8,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11746905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004436","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 genomic analyses combined with molecular dynamics simulations reveal the impact of deleterious mutations of Bcl-2 gene on the apoptotic machinery and implications in carcinogenesis.","authors":"Ghazi Elamin, Zhichao Zhang, Depika Dwarka, Kabange Kasumbwe, John Mellem, Nompumelelo P Mkhwanazi, Paradise Madlala, Mahmoud E S Soliman","doi":"10.3389/fgene.2024.1502152","DOIUrl":"10.3389/fgene.2024.1502152","url":null,"abstract":"<p><strong>Objectives: </strong>Unlike other diseases, cancer is not just a genome disease but should broadly be viewed as a disease of the cellular machinery. Therefore, integrative multifaceted approaches are crucial to understanding the complex nature of cancer biology. Bcl-2 (B-cell lymphoma 2), encoded by the human BCL-2 gene, is an anti-apoptotic molecule that plays a key role in apoptosis and genetic variation of Bcl-2 proteins and is vital in disrupting the apoptotic machinery. Single nucleotide polymorphisms (SNPs) are considered viable diagnostic and therapeutic biomarkers for various cancers. Therefore, this study explores the association between SNPs in Bcl-2 and the structural, functional, protein-protein interactions (PPIs), drug binding and dynamic characteristics.</p><p><strong>Methods: </strong>Comprehensive cross-validated bioinformatics tools and molecular dynamics (MD) simulations. Multiple sequence, genetic, structural and disease phenotype analyses were applied in this study.</p><p><strong>Results: </strong>Analysis revealed that out of 130 mutations, approximately 8.5% of these mutations were classified as pathogenic. Furthermore, two particular variants, namely, Bcl-2^G101V and Bcl-2^F104L, were found to be the most deleterious across all analyses. Following 500 ns, MD simulations showed that these mutations caused a significant distortion in the protein conformational, protein-protein interactions (PPIs), and drug binding landscape compared to Bcl-2^WT.</p><p><strong>Conclusion: </strong>Despite being a predictive study, the findings presented in this report would offer a perspective insight for further experimental investigation, rational drug design, and cancer gene therapy.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"15 ","pages":"1502152"},"PeriodicalIF":2.8,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004154","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: Craniofacial deafness hand syndrome with unusual cardiovascular symptoms and lack of holistic care.","authors":"Samantha Saenz Hinojosa, Carlos Reyes-Silva, Kazuyoshi Hosomichi, Vanessa I Romero","doi":"10.3389/fgene.2024.1354632","DOIUrl":"10.3389/fgene.2024.1354632","url":null,"abstract":"<p><strong>Background: </strong>Delays in diagnosing rare genetic disorders often arise due to limited awareness and systemic challenges in primary care. This case highlights the importance of a holistic approach to patient care, encompassing timely detection and comprehensive evaluation of clinical features.</p><p><strong>Methods: </strong>We report the case of a 21-year-old Ecuadorian male with facial and hand dysmorphias, cardiomegaly, pulmonary hypertension, and patent ductus arteriosus (PDA). Whole-exome sequencing, performed using the Illumina NextSeq platform. We extensively analyzed over 100 genes linked to congenital structural heart diseases.</p><p><strong>Results: </strong>The genetic findings provided a definitive diagnosis of Craniofacial-Deafness-Hand Syndrome, an extremely rare autosomal dominant condition, but found no variants that explain the patient's cardiac phenotype. We identified a novel pathogenic missense variant in the <i>PAX3</i> gene (c.A91C, p. T31P).</p><p><strong>Discussion and conclusions: </strong>This case underscores the necessity of integrating genetic testing into routine clinical practice to enhance diagnostic precision for rare diseases. It also highlights the need for multidisciplinary collaboration and a holistic care model to improve patient outcomes. The unique association of Craniofacial-Deafness-Hand Syndrome with cardiovascular anomalies due to a <i>PAX3</i> variation provides valuable insights into the genetic underpinnings of this rare condition.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"15 ","pages":"1354632"},"PeriodicalIF":2.8,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028287","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}