BMC Medical Genomics最新文献

{"title":"A real-time PCR-based noninvasive prenatal RHD screening assay optimized for population-specific RHD allelic spectra in China.","authors":"Xiang Wei, Linzhi Jiang, Qian Zhu","doi":"10.1186/s12920-026-02337-2","DOIUrl":"10.1186/s12920-026-02337-2","url":null,"abstract":"<p><strong>Background: </strong>Prenatal RhD screening enables risk stratification for RhD-associated hemolytic disease of the fetus and newborn (HDFN) and supports rational，evidence-based use of prophylactic anti-RhD immunoglobulin. However, noninvasive prenatal RhD screening remains challenging in the Chinese population, primarily due to population-specific RHD allelic diversity and the limited adaptability of current assay designs.</p><p><strong>Methods: </strong>We developed and optimized a real-time PCR-based assay for noninvasive prenatal RHD genotyping, specifically designed to accommodate the spectrum of clinically relevant RHD alleles in the Chinese population. By simultaneously targeting RHD exons 5, 9, and 10, the assay enables detection of paternally inherited RHD alleles within a single analytical workflow. This assay facilitates accurate fetal RHD status determination in pregnancies involving the predominant RhD-negative alleles, including RHD*01N.01, RHD*01N.03, and RHD*01EL.01.</p><p><strong>Results: </strong>The assay accurately predicted fetal RHD status across all simulated maternal genotypes, including those carrying non-deletion alleles such as RHD*01N.03 and RHD*01EL.01.</p><p><strong>Conclusion: </strong>This study presents a methodological framework for noninvasive prenatal RHD genotyping, specifically optimized for Chinese and other East Asian populations. Assay performance relies on distinct amplification patterns of population-specific RHD alleles across exons 5, 9, and 10. In addition, inclusion of exon 5 allows detection of RHD variants frequently observed in African populations, suggesting potential applicability across genetically diverse populations, pending further population-specific validation.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"19 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13452092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148697033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and pilot testing of a prostate cancer polygenic risk report.","authors":"Julia N Griffin, Morgan E Danowski, Haley L Gerety, Katherine Lafferty, Marla L Clayman, Ashley A Antwi, Mercedes G Bertero, Charles A Brunette, Chris Gillespie, Louise Guentert, Niall J Lennon, Julian Martin, Lauren S Patel, Jason L Vassy","doi":"10.1186/s12920-026-02416-4","DOIUrl":"10.1186/s12920-026-02416-4","url":null,"abstract":"<p><strong>Background: </strong>Polygenic risk scores (PRS) are increasingly being incorporated into clinical care, yet optimal strategies for communicating PRS results to patients and clinicians remain undefined. Effective report design is critical to ensure comprehension and appropriate use, particularly for complex conditions such as prostate cancer where screening decisions are nuanced. We developed and pilot tested patient-facing materials to communicate integrated polygenic and monogenic risk for prostate cancer in the context of a randomized clinical trial.</p><p><strong>Methods: </strong>We designed a summary report and accompanying Frequently Asked Questions (FAQ) page to communicate prostate cancer genetic risk within the Prostate Cancer, Genetic Risk, and Equitable Screening Study (ProGRESS). Materials were developed through an iterative, multidisciplinary process informed by existing literature on genomic risk communication. We conducted semi-structured interviews with a national sample of eight men eligible for prostate cancer screening to evaluate comprehension, interpretation of visual elements, perceived usefulness, and preferences for improvement. Interviews were transcribed and analyzed using reflexive thematic analysis.</p><p><strong>Results: </strong>Participants generally found the summary report and FAQ page understandable and visually engaging. Graphical displays of absolute risk, particularly pictograph arrays, facilitated comprehension and helped contextualize risk. Visual cues such as color and bold formatting effectively directed attention to key information, with red coloring perceived as particularly salient for high-risk results. In contrast, more complex visualizations, including bell curves and incidence curves, were frequently misunderstood or not interpreted as intended. Participants expressed a desire for clearer guidance regarding next steps and additional accessible information, suggesting supplementary resources such as hyperlinks or QR codes. Concerns about readability included small font size and high text density.</p><p><strong>Conclusions: </strong>In this qualitative pilot study, patient-facing materials for communicating prostate cancer PRS were generally well received, with specific design features such as simple visualizations and clear formatting enhancing understanding. Findings highlight the importance of intuitive risk displays and actionable guidance in PRS reporting. These results provide practical insights to inform the design of genomic risk reports as PRS-based prostate cancer screening approaches move toward clinical implementation.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT05926102; date of registry: July 3, 2023.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"19 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13520487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficient differential latent network analysis: applications to colon cancer.","authors":"Yewon Han, Lee Sael","doi":"10.1186/s12920-026-02433-3","DOIUrl":"10.1186/s12920-026-02433-3","url":null,"abstract":"<p><strong>Background: </strong>Colon cancer (CC) presents significant molecular heterogeneity, complicating our understanding of its initiation and progression. Identifying CC-associated genes and their interactions is crucial for improving diagnostics and therapeutics. However, current gene analysis methods struggle to holistically capture complex gene interactions due to their inherent complexity.</p><p><strong>Method: </strong>We propose a novel, simple, and scalable method called EFFICIENT DIFFERENTIAL LATENT NETWORK ANALYSIS (EDLNA) for detecting alterations in gene interactions using latent co-expression patterns. Our approach applies non-negative matrix factorization to construct separate latent gene networks for normal and cancer samples. We then identify differential interactions, followed by protein-protein interaction network and transcription factor (TF) analyses to detect functional modules and regulatory relationships.</p><p><strong>Results: </strong>We evaluated EDLNA against conventional methods using both simulated and colon cancer gene expression data (GSE44076, GSE50760). In simulation studies, EDLNA was significantly faster among differential network analysis techniques while maintaining comparable accuracy. When applied to colon cancer data, our method outperformed differential gene expression analysis in identifying biologically relevant gene clusters and stage-specific traits.</p><p><strong>Conclusions: </strong>EDLNA provides an efficient and scalable framework for identifying stage-specific gene interactions that bridge molecular mechanisms with clinical phenotypes. These findings underscore its potential for discovering novel biomarkers and advancing targeted therapies in colon cancer.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"19 Suppl 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13410580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148598554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and functional characterization of a SUZ12 frameshift variant in a Chinese family with Imagawa-Matsumoto syndrome.","authors":"Xin Xu, Hong Xu, Songming Huang, Yikang He, Ling Zhang","doi":"10.1186/s12920-026-02431-5","DOIUrl":"https://doi.org/10.1186/s12920-026-02431-5","url":null,"abstract":"<p><strong>Background: </strong>Imagawa-Matsumoto syndrome (IMMAS) is a rare overgrowth disorder caused by heterozygous loss-of-function variants in SUZ12, which encodes a core subunit of the Polycomb Repressive Complex 2 (PRC2). To date, fewer than 20 cases have been reported, and the molecular mechanisms underlying PRC2 dysfunction in IMMAS remain incompletely understood.</p><p><strong>Methods: </strong>Trio-based whole-exome sequencing (Trio-WES) was performed in a Chinese family presenting with overgrowth and dysmorphic features. The candidate variant was validated by Sanger sequencing and segregation analysis. AlphaFold 3 was used to predict the structural consequences of the variant. In vitro overexpression and protein assays were conducted to evaluate SUZ12 protein expression and subcellular localization.</p><p><strong>Results: </strong>The proband exhibited global developmental delay, macrocephaly, hypertrichosis, and distinctive craniofacial dysmorphism. Trio-WES identified a heterozygous frameshift variant in SUZ12 (c.1244_1248del; p.Glu415GlyfsTer5). Computational modeling predicted that the truncating variant removes the ZnF and VEFS domains and may affect the predicted SUZ12-EZH2 interface. In vitro expression of the mutant construct confirmed the production of a truncated SUZ12 protein. Furthermore, peripheral blood mononuclear cells (PBMCs) from both the proband and her mother showed a substantial global reduction in H3K27me3 levels, consistent with impaired PRC2-mediated histone methylation in vivo.</p><p><strong>Conclusions: </strong>We report a Chinese family with Imagawa-Matsumoto syndrome harboring a SUZ12 frameshift variant (c.1244_1248del; p.Glu415GlyfsTer5). Our study expands the phenotypic spectrum associated with this variant and provides evidence consistent with impaired PRC2-mediated histone methylation.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"19 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13471259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benchmarking sequence-based and AlphaFold-based methods for pMHC-II binding core prediction: distinct strengths and consensus approaches.","authors":"Soobon Ko, Honglan Li, Hongeun Kim, Woong-Hee Shin, Junsu Ko, Yoonjoo Choi","doi":"10.1186/s12920-026-02432-4","DOIUrl":"10.1186/s12920-026-02432-4","url":null,"abstract":"<p><strong>Background: </strong>Interactions between peptide and MHC class II (pMHC-II) are crucial for T-cell recognition and immune responses, as MHC-II molecules present peptide fragments to T cells, enabling the distinction between self and non-self antigens. Accurately predicting the pMHC-II binding core is particularly important because it provides insights into pMHC-II interactions and T-cell receptor engagement. Given the high polymorphism and peptide-binding promiscuity of MHC-II molecules, computational prediction methods are essential for understanding pMHC-II interactions. While sequence-based methods are widely used, recent advances in AlphaFold-based structure prediction have opened new possibilities for improving pMHC-II binding core predictions.</p><p><strong>Methods: </strong>We constructed a non-redundant dataset of 72 pMHC-II complexes from the IMGT database, supplemented with shuffled negative peptides and curated non-binders. Two sequence-based methods (NetMHCIIpan-4.3 and DeepMHCII) and two structure-based methods (AlphaFold2 fine-tuned (AF-FT) and AlphaFold3 (AF3)) were benchmarked for binding and core prediction. Performance was evaluated using standard metrics (precision, recall, F1 score), and consensus strategies integrating sequence- and structure-based models were developed for scenarios with known and unknown binding status.</p><p><strong>Results: </strong>The AlphaFold-based methods showed strong performance in predicting positive binders, with AF3 achieving the highest positive recall (0.86) and AF2-FT performing similarly (0.81). However, both methods frequently misclassified unbound peptides as binders. NetMHCIIpan excelled at identifying non-binders, achieving the highest negative recall (0.93), but had lower positive recall (0.44). In contrast, DeepMHCII demonstrated moderate performance without any notable strength. Consensus approaches combining AlphaFold-based methods for binder identification with filtering using NetMHCIIpan improved overall prediction precision (0.94 and 0.87 for known and unknown binding status, respectively).</p><p><strong>Conclusions: </strong>This study highlights the complementary strengths of AlphaFold-based and sequence-based methods for predicting pMHC-II binding core regions. AlphaFold-based methods excel in predicting positive binders, while NetMHCIIpan is highly effective at identifying non-binders. Future research should focus on improving the prediction of unbound peptides for AlphaFold-based models. Since NetMHCIIpan's binding core predictive ability is already high, future efforts should concentrate on enhancing its binding prediction to further improve overall accuracy.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"19 Suppl 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13410576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148598572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breakpoint-level characterization of a novel CEP290 tandem duplication in trans with a pathogenic splice-site variant in a patient with Leber congenital amaurosis.","authors":"Shumei Xu, Jia Geng, Wenyu Xiong, Man Liu, Chao Wang, Xiaolu Wang, Ting Tang, Qian Zhang, Huijun Yuan, Yu Lu","doi":"10.1186/s12920-026-02435-1","DOIUrl":"https://doi.org/10.1186/s12920-026-02435-1","url":null,"abstract":"<p><strong>Background: </strong>Inherited retinal degenerations are a group of genetically heterogeneous disorders characterized by progressive photoreceptor degeneration. Despite the widespread use of targeted gene panels and exome sequencing, many cases remain genetically unresolved because structural and other complex variants may be missed. CEP290 is a major cause of early-onset retinal degeneration, and although most pathogenic variants are sequence-level changes, structural rearrangements have increasingly been recognized through genome-wide sequencing approaches. This study aimed to identify the genetic cause in a child with early-onset retinal degeneration and to characterize the molecular mechanism of the underlying variant.</p><p><strong>Methods: </strong>A 4-year-old boy with presumed rod-cone dystrophy underwent comprehensive clinical evaluation and trio whole-genome sequencing. Compound heterozygous CEP290 variants, consisting of a maternally inherited splice-site variant and a paternally inherited large intragenic duplication, were identified and evaluated. The duplication breakpoint was subsequently characterized by structural variant analysis, gap-PCR, and Sanger sequencing, followed by analysis of breakpoint-associated microhomology, GC content, and repeat elements. Variants were interpreted according to ACMG/AMP and ClinGen recommendations, as appropriate.</p><p><strong>Results: </strong>Trio-WGS detected compound heterozygous CEP290 variants: a maternal splice-site variant c.6012-2 A > G and a paternal exons 31-53 tandem duplication (chr12:88050034-88089159dup). Gap-PCR and Sanger sequencing validated this rearrangement and defined a 7-bp junction microhomology (AAATTCT). Breakpoint analysis showed low GC and abundant repeats, supporting FoSTeS/MMBIR as the causal replicative mechanism. This duplication is predicted to alter CEP290 transcripts, triggering frameshift, premature termination and C-terminal domain loss.</p><p><strong>Conclusions: </strong>To our knowledge, this study represents the first breakpoint-resolved characterization of a pathogenic CEP290 tandem duplication encompassing exons 31-53 identified in compound heterozygosity with a pathogenic splice-site variant in a patient with early-onset retinal degeneration. The duplication is predicted to disrupt the CEP290 coding sequence, resulting in a frameshift, premature termination codon, and loss of the C-terminal functional domain. These findings expand the spectrum of pathogenic structural variants in CEP290 and underscore the value of whole-genome sequencing and breakpoint-level analysis for resolving genetically unexplained inherited retinal disorders.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148547605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DR.DEGMON: self-explainable deep neural network for drug-induced cell viability prediction incorporating differentially expressed genes and gene ontology.","authors":"Wootaek Lim, Jitae Kim, Songhyeon Kim, Hyunsu Bong, Kwang-Su Park, Minji Jeon","doi":"10.1186/s12920-026-02434-2","DOIUrl":"10.1186/s12920-026-02434-2","url":null,"abstract":"<p><strong>Background: </strong>Accurate prediction of cancer drug responses is essential for advancing cancer treatment strategies and drug development. With the increasing availability of large-scale pharmacogenomic datasets, many deep learning models have been proposed to predict cancer drug responses. However, many existing models lack the capacity to offer critical biomedical insights, such as providing interpretability regarding the potential mechanism of action.</p><p><strong>Methods: </strong>We propose DR.DEGMON (Drug Response prediction using Differentially Expressed Genes with Multi-layer perceptron integrating gene Ontology Network), a self-explainable deep neural network designed to predict the viability of pan-cancer cell lines in response to drug treatments by utilizing differentially expressed genes. DR.DEGMON leverages prior biological knowledge by incorporating Gene Ontology (GO) into the hierarchical structure of a multi-layer perceptron. The architecture of DR.DEGMON highlights key genes and GO terms that contribute to drug responses through layer-wise relevance propagation (LRP), suggesting potential biological pathways associated with specific drugs.</p><p><strong>Results: </strong>DR.DEGMON achieved a Pearson correlation coefficient of 0.8568 for cell viability prediction, outperforming all baseline models. The model also showed robust generalization performance on external datasets, including GDSC, PRISM, and CCLE. In addition, we employed layer-wise relevance propagation (LRP) to obtain relevance scores for input genes and nodes representing GO terms.</p><p><strong>Conclusion: </strong>DR.DEGMON shows high performance in predicting drug responses and provides interpretable results. The integration of GO and LRP enabled the model to suggest the underlying biological processes involved in drug responses, making it a valuable tool for predicting outcomes and discovering new biomedical knowledge in cancer pharmacogenomics. This approach offers both practical utility in drug development and a method for improving the understanding of cancer biology.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13410581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148547593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The infero-apical left ventricular aneurysm and long QT syndrome caused by mutation delKKP 1504-1506 in SCN5A gene.","authors":"Zhijuan Lu, Jiadong Lin, Yi Chen, Xiuli Zhou, Liping Lin, Xiaocong Zhang, Qiang Wang, Xinsheng Huang","doi":"10.1186/s12920-026-02428-0","DOIUrl":"https://doi.org/10.1186/s12920-026-02428-0","url":null,"abstract":"<p><strong>Background: </strong>Long QT syndrome (LQTS) is considered a primary cardiac ion channelopathy. Several studies have shown that myocardial functional alterations may occur in patients with LQTS type 3 (LQT3). However, it is currently unclear whether there is a specific relationship between phenotype and genotype. The aim of this study is to provide additional information on the phenotype and genotype of LQT3 caused by a novel delKKP 1504-1506 mutation in a Chinese family.</p><p><strong>Case presentation: </strong>The family came to our attention because of a sustained corrected QT interval (QTc) prolongation in a 14-year-old girl who had experienced a loss of consciousness with Mobitz type II atrioventricular block one year earlier. Three family members carrying the delKKP 1504-1506 mutation demonstrated a combination of infero-apical left ventricular aneurysms and prolonged QTc, and two members showed J-waves in the right precordial lead V2.</p><p><strong>Conclusions: </strong>This case suggests that the delKKP 1504-1506 mutation in SCN5A may not only lead to impaired impulse propagation in the conduction system and a prolonged QTc, but may also be associated with infero-apical ventricular aneurysms and J-wave syndromes, possibly corresponding to regional myocardial fibrosis.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gender-wise distribution of metabolic risk factors and their relationship with fibroblast growth factor 1 and gene polymorphism (rs152524).","authors":"Saima Naz Mohsin, Faiza Saleem, Natasha Waheed, Hira Ashfaq, Ambreen Muddassir, Ayesha Humayun","doi":"10.1186/s12920-026-02427-1","DOIUrl":"https://doi.org/10.1186/s12920-026-02427-1","url":null,"abstract":"<p><strong>Background: </strong>Non-communicable diseases (NCDs) account for over 70% of deaths worldwide, and metabolic risk factors such as obesity, dyslipidemia, and hypertension greatly increase the incidence of NCDs. Lifestyle changes have exacerbated these conditions in Pakistan; therefore, a better knowledge of their underlying mechanisms is required. This study investigates the relationship between fibroblast growth factor 1 (FGF1) blood levels, the rs152524 gene polymorphism, and metabolic risk factors.</p><p><strong>Method: </strong>We conducted a hospital-based, cross-sectional study of 199 adults recruited from outpatient departments between September 2023 and June 2024. After written informed consent, demographic, medical, and biochemical data were collected. FGF1 rs152524 was genotyped using tetra-primer ARMS PCR and serum FGF1 levels were quantified by ELISA at the National Health Research Complex and Lahore College for Women University. Statistical analyses were performed using SPSS v.26; p < 0.05 was considered significant.</p><p><strong>Results: </strong>There were no significant differences in age or BMI between males and females. However, females demonstrated significantly higher median (IQR) of FGF1 levels [333 pg/ml (250-467) vs. 292 pg/ml (212-374); p = 0.011]. Fasting blood glucose, LDL-cholesterol and hypertension were the three main predictors of FGF1 levels, according to regression analysis. Within the participant population, 38.7% carried the AA genotype of rs152524. The allelic frequencies of reference A and alternative G alleles were 0.5955 and 0.4045 respectively. AA genotype was substantially associated with both hypertension (p < 0.001) and overweight/obesity (p = 0.002). The highest median (IQR) FGF1 blood levels 351(263-546) pg/ml were observed among AA genotype carriers. At the same time, a substantial rise in HDL-cholesterol 36(32-42) was found among carriers of the GG genotype.</p><p><strong>Conclusion: </strong>This hospital-based study identified a potential association between the FGF1 rs152524 AA genotype and obesity and hypertension. The AA genotype was present in 38% of participants, with risk rising per 'A' allele, while the G allele appeared protective. These preliminary findings require validation in larger, population-based cohorts before clinical relevance can be assessed.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148434936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and molecular characterization of TCF12 variants in an Asian pediatric cohort with craniosynostosis.","authors":"Rongle Zhong, Lei Zheng, Qing Yan, Zhe Gao, Chunyu Zhong, Xianli Zhang, Bixia Zheng, Ling Zhang, Wei Zhou, Gang Wang","doi":"10.1186/s12920-026-02417-3","DOIUrl":"10.1186/s12920-026-02417-3","url":null,"abstract":"<p><strong>Background: </strong>Craniosynostosis is a genetically heterogeneous craniofacial disorder caused by the premature fusion of one or more cranial sutures. Pathogenic variants in TCF12, encoding a basic helix-loop-helix (bHLH) transcription factor, represent a major cause of autosomal dominant coronal craniosynostosis and are characterized by incomplete penetrance and marked phenotypic variability. However, clinical and molecular data from Asian pediatric populations remain limited.</p><p><strong>Methods: </strong>Trio-based whole-exome sequencing was performed on ten pediatric patients with cranial deformities and their parents. The identified TCF12 variants were classified according to the American College of Medical Genetics and Genomics (ACMG) guidelines and validated by Sanger sequencing. Detailed clinical and radiological data were collected. In addition, a comprehensive literature review was conducted to summarize previously reported TCF12 variants and associated phenotypes.</p><p><strong>Results: </strong>Ten distinct heterozygous TCF12 variants were identified in ten unrelated pediatric patients, all of which were classified as pathogenic or likely pathogenic according to ACMG criteria. Six variants were inherited, and four occurred de novo. Seven patients had imaging-confirmed craniosynostosis, predominantly involving the coronal sutures (five bilateral and one unilateral), while one patient presented with multisuture craniosynostosis (left coronal and sagittal sutures). Three patients showed cranial deformities without radiographic evidence of suture fusion. Phenotypic heterogeneity and incomplete penetrance were observed, including a mildly affected parent. Most pathogenic variants were truncating variants distributed mainly across exons 14-19 and predicted to induce loss of function, either through nonsense-mediated mRNA decay or the production of truncated proteins lacking the entire C-terminal bHLH domain. Structural modeling analysis further indicated that the bHLH-domain-located missense variant p.Arg603Trp alters the local DNA-binding conformation of TCF12 and impairs its binding affinity to the E-box DNA motif.</p><p><strong>Conclusions: </strong>This study provides additional clinical and molecular data on TCF12-related craniosynostosis in a pediatric cohort from an Asian population. Our findings support haploinsufficiency as the central pathogenic mechanism, primarily driven by truncating variants affecting the C-terminal bHLH domain. The marked clinical heterogeneity, the presence of mild or evolving phenotypes, and incomplete penetrance observed in our cohort underscore the importance of early diagnosis and longitudinal clinical surveillance in affected families.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13520298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148434985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}