BMC Medical Genomics最新文献

{"title":"Drug-target binding affinity prediction based on power graph and word2vec.","authors":"Jing Hu, Shuo Hu, Minghao Xia, Kangxing Zheng, Xiaolong Zhang","doi":"10.1186/s12920-024-02073-5","DOIUrl":"10.1186/s12920-024-02073-5","url":null,"abstract":"<p><strong>Background: </strong>Drug and protein targets affect the physiological functions and metabolic effects of the body through bonding reactions, and accurate prediction of drug-protein target interactions is crucial for drug development. In order to shorten the drug development cycle and reduce costs, machine learning methods are gradually playing an important role in the field of drug-target interactions.</p><p><strong>Results: </strong>Compared with other methods, regression-based drug target affinity is more representative of the binding ability. Accurate prediction of drug target affinity can effectively reduce the time and cost of drug retargeting and new drug development. In this paper, a drug target affinity prediction model (WPGraphDTA) based on power graph and word2vec is proposed.</p><p><strong>Conclusions: </strong>In this model, the drug molecular features in the power graph module are extracted by a graph neural network, and then the protein features are obtained by the Word2vec method. After feature fusion, they are input into the three full connection layers to obtain the drug target affinity prediction value. We conducted experiments on the Davis and Kiba datasets, and the experimental results showed that WPGraphDTA exhibited good prediction performance.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 Suppl 1","pages":"9"},"PeriodicalIF":2.1,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977392","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":"Challenges of reproducible AI in biomedical data science.","authors":"Henry Han","doi":"10.1186/s12920-024-02072-6","DOIUrl":"10.1186/s12920-024-02072-6","url":null,"abstract":"<p><p>Artificial intelligence (AI) is revolutionizing biomedical data science at an unprecedented pace, transforming various aspects of the field with remarkable speed and depth. However, a critical issue remains unclear: how reproducible are the AI models and systems employed in biomedical data science? In this study, we examine the challenges of AI reproducibility by analyzing the factors influenced by data, model, and learning complexities, as well as through a game-theoretical perspective. While adherence to reproducibility standards is essential for the long-term advancement of AI, the conflict between following these standards and aligning with researchers' personal goals remains a significant hurdle in achieving AI reproducibility.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 Suppl 1","pages":"8"},"PeriodicalIF":2.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11724458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963484","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":"A machine learning model and identification of immune infiltration for chronic obstructive pulmonary disease based on disulfidptosis-related genes.","authors":"Sijun Li, Qingdong Zhu, Aichun Huang, Yanqun Lan, Xiaoying Wei, Huawei He, Xiayan Meng, Weiwen Li, Yanrong Lin, Shixiong Yang","doi":"10.1186/s12920-024-02076-2","DOIUrl":"10.1186/s12920-024-02076-2","url":null,"abstract":"<p><strong>Background: </strong>Chronic obstructive pulmonary disease (COPD) is a chronic and progressive lung disease. Disulfidptosis-related genes (DRGs) may be involved in the pathogenesis of COPD. From the perspective of predictive, preventive, and personalized medicine (PPPM), clarifying the role of disulfidptosis in the development of COPD could provide a opportunity for primary prediction, targeted prevention, and personalized treatment of the disease.</p><p><strong>Methods: </strong>We analyzed the expression profiles of DRGs and immune cell infiltration in COPD patients by using the GSE38974 dataset. According to the DRGs, molecular clusters and related immune cell infiltration levels were explored in individuals with COPD. Next, co-expression modules and cluster-specific differentially expressed genes were identified by the Weighted Gene Co-expression Network Analysis (WGCNA). Comparing the performance of the random forest (RF), support vector machine (SVM), generalized linear model (GLM), and eXtreme Gradient Boosting (XGB), we constructed the ptimal machine learning model.</p><p><strong>Results: </strong>DE-DRGs, differential immune cells and two clusters were identified. Notable difference in DRGs, immune cell populations, biological processes, and pathway behaviors were noted among the two clusters. Besides, significant differences in DRGs, immune cells, biological functions, and pathway activities were observed between the two clusters.A nomogram was created to aid in the practical application of clinical procedures. The SVM model achieved the best results in differentiating COPD patients across various clusters. Following that, we identified the top five genes as predictor genes via SVM model. These five genes related to the model were strongly linked to traits of the individuals with COPD.</p><p><strong>Conclusion: </strong>Our study demonstrated the relationship between disulfidptosis and COPD and established an optimal machine-learning model to evaluate the subtypes and traits of COPD. DRGs serve as a target for future predictive diagnostics, targeted prevention, and individualized therapy in COPD, facilitating the transition from reactive medical services to PPPM in the management of the disease.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"7"},"PeriodicalIF":2.1,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11715737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142943649","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":"Whole-exome sequencing uncovers the genetic basis of hereditary concomitant exotropia in ten Chinese pedigrees.","authors":"Wenhua Duan, Taicheng Zhou, Xiaoru Huang, Dongqiong He, Min Hu","doi":"10.1186/s12920-024-02078-0","DOIUrl":"10.1186/s12920-024-02078-0","url":null,"abstract":"<p><strong>Purpose: </strong>To explore possible pathogenic genes for concomitant exotropia using whole-exome sequencing.</p><p><strong>Methods: </strong>In this study, 47 individuals from 10 concomitant exotropia (including intermittent exotropia and constant exotropia) pedigrees were enrolled. Whole-exome sequencing was used to screen mutational profiles in 25 affected individuals and 10 unaffected individuals. Sanger sequencing and in silico analysis were performed for all participants. Two target genes were used to capture the sequences of 220 sporadic samples.</p><p><strong>Results: </strong>All 10 concomitant exotropia pedigrees presented autosomal dominant inheritance with childhood onset (3.35 ± 1.51 years old). Eleven different missense variants were identified among seven potential pathogenic genes (COL4A2, SYNE1, LOXHD1, AUTS2, GTDC2, HERC2 and CDH3) that cosegregated with pedigree members. All variants were predicted to be deleterious and had low frequencies in the general population. Distinct variants of COL4A2 were present in three pedigrees, and distinct variants of SYNE1 were present in two pedigrees. Fifteen variants in AUTS2 and four variants in GTDC2 were identified in 220 patients with sporadic concomitant exotropia using a target-capture sequencing approach.</p><p><strong>Conclusion: </strong>This is the first study to explore the genetic mechanism of concomitant exotropia and identify seven associated genes (COL4A2, SYNE1, LOXHD1, AUTS2, GTDC2, HERC2 and CDH3) that may be candidate genes causing concomitant exotropia. More samples and in-depth studies are needed to verify these findings.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"4"},"PeriodicalIF":2.1,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142943684","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":"Hypercalcemia and co-occurring TBX1 mutation in Glycogen Storage Disease Type Ib: case report.","authors":"Zakaria Kasmi, Imane Ain El Hayat, Zahra Aadam, Abderrahmane Errami, Ibtihal Benhsaien, Jalila El Bakkouri, Dalal Ben Sabbahia, Meryem Atrassi, Ahmed Aziz Bousfiha, Fatima Ailal","doi":"10.1186/s12920-024-02057-5","DOIUrl":"10.1186/s12920-024-02057-5","url":null,"abstract":"<p><p>Glycogen Storage Disease Type Ib (GSD-Ib) is a rare autosomal recessive metabolic disorder caused by mutations in SLC37A4, leading to a deficiency in glucose-6-phosphate translocase. This disorder is characterized by impaired glycogenolysis and gluconeogenesis, resulting in clinical and metabolic manifestations. We report a three-month-old Moroccan female patient presenting with doll-like facies, hepatomegaly, dysmorphic features, and developmental delays. Laboratory analysis revealed hypoglycemia, elevated triglyceride levels, hypercalcemia, and neutropenia. Genetic testing confirmed a homozygous pathogenic variant in SLC37A4 and a heterozygous variant of uncertain significance in TBX1. Initial management included a lactose-free and galactose-free diet, multivitamin supplementation, and granulocyte colony-stimulating factor (G-CSF) therapy to address neutropenia. A novel aspect of this case involves hypercalcemia as an unusual finding in GSD-Ib and the co-occurrence of a variant in the TBX1 gene, which is not typically associated with the disease but may contribute to the patient's clinical presentation. These findings add a new dimension to our understanding of GSD-Ib and suggest potential avenues for future research to elucidate these genetic interactions and their impact on clinical outcomes.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"5"},"PeriodicalIF":2.1,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11708236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055780","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":"Discovering the interactome, functions, and clinical relevance of enhancer RNAs in kidney renal clear cell carcinoma.","authors":"Zhaohui Sun, Haojie Du, Xudong Zheng, Hepeng Zhang, Huajie Hu","doi":"10.1186/s12920-024-02081-5","DOIUrl":"https://doi.org/10.1186/s12920-024-02081-5","url":null,"abstract":"<p><p>Enhancer RNA (eRNA) has emerged as a key player in cancer biology, influencing various aspects of tumor development and progression. In this study, we investigated the role of eRNAs in kidney renal clear cell carcinoma (KIRC), the most common subtype of renal cell carcinoma. Leveraging high-throughput sequencing data and bioinformatics analysis, we identified differentially expressed eRNAs in KIRC and constructed eRNA-centric regulatory networks. Our findings revealed that up-regulated eRNAs in KIRC potentially regulate immune response and hypoxia pathways, while down-regulated eRNAs may impact ion transport, cell cycle, and metabolism. Furthermore, we developed a diagnostic prediction model based on eRNA expression profiles, demonstrating its effectiveness in KIRC diagnosis. Finally, we elucidated the regulatory mechanism of an eRNA (ENSR00000305834) on the expression of SLC15A2, a potential prognostic biomarker in KIRC, through bioinformatics analysis and in vitro validation experiments. In summary, Our study highlights the clinical significance of eRNAs in KIRC and underscores their potential as therapeutic targets.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"3"},"PeriodicalIF":2.1,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926369","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":"Integrative analyses of mendelian randomization and bioinformatics reveal casual relationship and genetic links between COVID-19 and knee osteoarthritis.","authors":"Xiao Zheng, Jinhao Li, Qinfeng Ma, Jianping Gong, Jianbo Pan","doi":"10.1186/s12920-024-02074-4","DOIUrl":"10.1186/s12920-024-02074-4","url":null,"abstract":"<p><strong>Background: </strong>Clinical and epidemiological analyses have found an association between coronavirus disease 2019 (COVID-19) and knee osteoarthritis (KOA). Infection with COVID-19 may increase the risk of developing KOA.</p><p><strong>Objectives: </strong>This study aimed to investigate the potential causal relationship between COVID-19 and KOA using Mendelian randomization (MR) and to explore the underlying mechanisms through a systematic bioinformatics approach.</p><p><strong>Methods: </strong>Our investigation focused on exploring the potential causal relationship between COVID-19, acute upper respiratory tract infection (URTI) and KOA utilizing a bidirectional MR approach. Additionally, we conducted differential gene expression analysis using public datasets related to these three conditions. Subsequent analyses, including transcriptional regulation analysis, immune cell infiltration analysis, single-cell analysis, and druggability evaluation, were performed to explore potential mechanisms and prioritize therapeutic targets.</p><p><strong>Results: </strong>The results indicate that COVID-19 has a one-way impact on KOA, while URTI does not play a causal role in this association. Ribosomal dysfunction may serve as an intermediate factor connecting COVID-19 with KOA. Specifically, COVID-19 has the potential to influence the metabolic processes of the extracellular matrix, potentially impacting the joint homeostasis. A specific group of genes (COL10A1, BGN, COL3A1, COMP, ACAN, THBS2, COL5A1, COL16A1, COL5A2) has been identified as a shared transcriptomic signature in response to KOA with COVID-19. Imatinib, Adiponectin, Myricetin, Tranexamic acid, and Chenodeoxycholic acid are potential drugs for the treatment of KOA patients with COVID-19.</p><p><strong>Conclusions: </strong>This study uniquely combines Mendelian randomization and bioinformatics tools to explore the possibility of a causal relationship and genetic association between COVID-19 and KOA. These findings are expected to provide novel perspectives on the underlying biological mechanisms that link COVID-19 and KOA.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"2"},"PeriodicalIF":2.1,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920611","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":"Bioinformatics analysis of miR-2861 and miR-5011-5p that function as potential tumor suppressors in colorectal carcinogenesis.","authors":"Alper Aytekin, Hikmet Kadakal, Deniz Mihcioglu, Turkan Gurer","doi":"10.1186/s12920-024-02080-6","DOIUrl":"10.1186/s12920-024-02080-6","url":null,"abstract":"<p><strong>Background: </strong>The study aimed to was to investigate the relationship between miR-2861, miR-5011-5p, and colorectal carcinogenesis.</p><p><strong>Method: </strong>In the present study, it was isolated RNA from both the tumor and non-tumor tissue of a total of 80 CRC patients and after synthesizing the cDNA, it was performed qRT-PCR to determine the expression levels of miR‑2861 and miR‑5011-5p. In addition, it was predicted that dysregulated miRNAs targets, pathways and functional gene annotations that may be important in colorectal carcinogenesis using KEGG pathway and GO analysis.</p><p><strong>Results: </strong>The resulting data revealed that both expression levels of miR-2861 and miR-5011-5p were significantly decreased in tumor tissues compared with non-tumor tissues of CRC patients. The GO and KEGG pathway analysis showed that miR-2861 and miR-5011-5p may participate in multiple the biological process, cellular components, and molecular function subcategories such as mitotic cell cycle, regulation of small GTPase mediated signal transduction, cell death, and acid binding transcription factor activity. It was also revealed that target genes of miRNAs can be found in signaling pathways such as TGF-beta, Rap1, Ras, cAMP, Wnt, mTOR and, PI3K-Akt signaling pathways.</p><p><strong>Conclusion: </strong>These findings imply that miR-2861 and miR-5011-5p might function as tumor suppressors in the development of CRC.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"1"},"PeriodicalIF":2.1,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920607","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":"Genetic analysis of partial duplication of the long arm of chromosome 16.","authors":"Dan Tang, Ai Chen, Jing Xu, Yu Huang, Jun Fan, Jin Wang, Hui Zhu, Guanghuan Pi, Li Yang, Fu Xiong, Zemin Luo, Gen Li, Lan Zeng, Shuyao Zhu","doi":"10.1186/s12920-024-02059-3","DOIUrl":"10.1186/s12920-024-02059-3","url":null,"abstract":"<p><strong>Background: </strong>Pure partial trisomy 16q12.1q22.1 is a rare chromosome copy number variant (CNV). The primary clinical phenotypes associated with this syndrome include abnormal facial morphology, global developmental delay (GDD), short stature, and reported predisposing factors for atypical behavior, autism, the development of learning disabilities, and neuropsychiatric disorders. The dosage-sensitive genes associated with partial trisomy are not disclosed preventing to establish a genotype-phenotype correlation.</p><p><strong>Methods: </strong>We report a case of a Chinese patient diagnosed with GDD and an abnormal facial shape, who was found to have partial trisomy 16 through karyotyping and high-throughput sequencing analysis. Karyotype and CNV tracing analyses were also conducted on the biological parents of the patient to assess for any chromosomal structural abnormalities. Additionally, we included 29 patients with pure partial trisomy 16q, reported in the DECIPHER database and the literature. We and performed a genotype-phenotype correlation analysis.</p><p><strong>Results: </strong>The proband, a 2-year-old female, was found to have a de novo 21.96 Mb duplication located between 16q12.1q22.1, with no other deletions observed on other chromosomes, indicating a pure partial trisomy of 16q. Through genotype and phenotype analysis of 29 individuals, we found that patients with the duplicated region located at the distal region of 16q may exhibit more severe symptoms than those with duplication at the proximal region; however, no relationship was identified between phenotype and the size of the duplicated segment.</p><p><strong>Conclusion: </strong>We report, for the first time, a patient with partial trisomy 16q validated by multiple genetic tests, including CNV-seq, whole exome sequencing (WES), and karyotyping. It is speculated that partial trisomy of 16q may be associated with continuous gene duplication. However, functional studies are necessary to identify the causative gene or critical region linked to duplication syndrome of chromosome 16q.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"294"},"PeriodicalIF":2.1,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881153","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":"Clinical characteristics and genetic analysis of four pediatric patients with Kleefstra syndrome.","authors":"Rong Ren, Yedan Liu, Peipei Liu, Jing Zhao, Mei Hou, Shuo Li, Zongbo Chen, Aiyun Yuan","doi":"10.1186/s12920-024-02065-5","DOIUrl":"10.1186/s12920-024-02065-5","url":null,"abstract":"<p><strong>Background: </strong>Kleefstra syndrome spectrum (KLEFS) is an autosomal dominant disorder that can lead to intellectual disability and autism spectrum disorders. KLEFS encompasses Kleefstra syndrome-1 (KLEFS1) and Kleefstra syndrome-2 (KLEFS2), with KLEFS1 accounting for more than 75%. However, limited information is available regarding KLEFS2. KLEFS1 is caused by a subtelomeric chromosomal abnormality resulting in either deletion at the end of the long arm of chromosome 9, which contains the EHMT1 gene, or by variants in the EHMT1 gene and the KMT2C gene that cause KLEFS2.</p><p><strong>Methods: </strong>This study was a retrospective analysis of clinical data from four patients with KLEFS. Exome sequencing (ES) and Sanger sequencing techniques were used to identify and validate the candidate variants, facilitating the analysis of genotype‒phenotype correlations of the EHMT1 and KMT2C genes. Protein structure modeling was performed to evaluate the effects of the variants on the protein's three-dimensional structure. In addition, real-time quantitative reverse transcription‒polymerase chain reaction (RT‒qPCR) and western blotting were used to examine the protein and mRNA levels of the KMT2C gene.</p><p><strong>Results: </strong>Two patients with KLEFS1 were identified: one with a novel variant (c.2382 + 1G > T) and the other with a previously reported variant (c.2426 C > T, p.Pro809Leu) in the EHMT1 gene. A De novo deletion at the end of the long arm of chromosome 9 was also reported. Furthermore, a patient with KLEFS2 was identified with a novel variant in the KMT2C gene (c.568 C > T, p.Arg190Ter). The RT‒qPCR and western blot results revealed that the expression of the KMT2C gene was downregulated in the KLEFS2 sample.</p><p><strong>Conclusion: </strong>This study contributes to the understanding of both KLEFS1 and KLEFS2 by identifying novel variants in EHMT1 and KMT2C genes, thereby expanding the variant spectrum. Additionally, we provide the first evidence of how a KMT2C variant leads to decreased gene and protein expression, enhancing our understanding of the molecular mechanisms underlying KLEFS2. Based on these findings, children exhibiting developmental delay, hypotonia, distinctive facial features, and other neurodevelopmental abnormalities should be considered for ES to ensure early intervention and treatment.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"290"},"PeriodicalIF":2.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11657243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852128","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}