BackgroundWiedemann-Steiner syndrome (WSS) is a genetic malformation syndrome caused by abnormalities in KMT2A. It is characterized by developmental delays, facial dysmorphism, hypertrichosis, failure to thrive, and musculoskeletal anomalies. Expanded applications of exome sequencing have increased the number of confirmed cases, broadening our understanding of the WSS spectrum.MethodsWe collected and organized the clinical and molecular features of 10 unrelated Korean patients diagnosed with WSS using molecular analysis. Clinical characteristics were presented based on the electronic medical records of the patients’ regular visits.ResultsSubject patients consisted of four male and six female patients. The median patient age at diagnosis was 6.76 years. In most cases, the chief complaint upon visiting a clinician was developmental delay (8/10). The most frequently observed phenotypes included failure to thrive (9/10), short stature (7/10), developmental delay (10/10), and hypertrichosis (10/10). The degree of developmental delay varied among the patients. The majority (9/10) were diagnosed by exome sequencing, with the exception of one patient (1/10) who had a microdeletion at 11q23.3, encompassing partial KMT2A, as diagnosed by chromosomal microarray. All patients had private pathogenic or Likely pathogenic variants without any recurrent variants, and nine of the 10 variants were novel.ConclusionsMost Korean patients with WSS exhibited suggestive features, but most were not pathognomonic of WSS; thus, many patients may only be identifiable by molecular analyses. Phenotypes frequently overlap with other chromatinopathy syndromes. Future studies are needed to determine the genetic background of patients with molecularly unresolved WSS and to further delineate WSS.

BackgroundDue to its predictable pharmacodynamics and pharmacokinetics, stable blood concentration, and relatively short half-life, rivaroxaban is widely used in the prevention and treatment of thrombosis. It nevertheless exhibits a certain level of inter-individual variability, and its safety concerns, including bleeding, are also becoming more noteworthy.Case presentationThis paper describes an elderly patient with nonvalvular atrial fibrillation that was complicated with coronary heart disease, who is a homozygous mutation carrier of the ABCB1 allele (rs1045642 C > T, rs1128503 C > T, rs2032582 G > T). He was developed severe gastrointestinal bleeding during administration of oral rivaroxaban combined with aspirin. We investigated the possible causes of the bleeding, and any potential correlation with the ABCB1 gene polymorphism, combined with antiplatelet drugs and anemia.ConclusionIn the treatment of patients with atrial fibrillation, doctors should pay close attention to drug interactions with antiplatelet agents in high-risk groups and closely monitor various examination indexes, including hemoglobin. In this case, bleeding might be potentially influenced by homozygous mutations in ABCB1, but more clinical data are needed to clarify the association between ABCB1 polymorphism and rivaroxaban pharmacokinetics and bleeding.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12920-025-02222-4.

Inflammatory cytokines are pivotal in the pathophysiology of acute coronary syndrome (ACS) and have been associated with major adverse cardiovascular events. In this study, we aimed to assess the association of eight polymorphisms in IL-10, IL-6, and TNF-α with the risk of ACS through a systematic review, meta-analysis, and trial sequential analysis. A comprehensive literature review was conducted across multiple databases, including PubMed/Medline, Web of Science, Scopus, and Cochrane Library, up until August 8, 2024. The Review Manager 5.3 software was utilized to compute the effect sizes such as the odds ratio accompanied by a 95% confidence interval. Out of 1499 records identified from databases, sources, or electronic searches, 51 articles were included in qualitative and quantitative syntheses (meta-analysis). For IL-6 -174G > C, the allelic and homozygous models showed significant associations with ACS risk. IL-6 -572G > C showed no significant association across all genetic models. IL-10 polymorphisms (-592C > A, -819C > T, and -1082A > G) generally showed no significant associations. TNF-α -308G > A polymorphism showed significant associations in all models. TNF-α -1031T > C and -238G > A showed no significant associations, with varying degrees of heterogeneity. Results suggest that certain cytokine polymorphisms, notably IL-6 -174G > C and TNF-α -308G > A, may play a crucial role in increasing susceptibility to ACS. These associations are especially pronounced in certain ethnic groups, such as Asians and Arabs, highlighting the importance of considering genetic diversity in clinical assessments.

Liver cancer is the leading cause of cancer deaths worldwide and is the only cancer type among the five deadliest cancers with an increasing incidence each year. The prognosis of liver cancer is poor and no effective treatment for this cancer to date. Arsenic sulfide has been found to be effective in the treatment of hematological malignancies but its therapeutic outcomes and associated mechanisms in liver cancer remain unknown. In this study, we found that arsenic sulfide treatment could effectively inhibit the proliferation, migration and promotion of apoptosis of hepatoma cell lines, and remarkably alleviated the progression of hepatocellular carcinoma in mouse models. Transcriptomic analysis of the HepG2 cell line treated with arsenic sulfide showed that arsenic sulfide inhibited the proliferation of hepatoma cells by inhibiting the expression of Triacylglycerol and Lipid Catabolism Deficient 1 (TLCD1), thereby alleviating the malignant progression of hepatocellular carcinoma. This study provides a molecular basis for arsenic sulfide in the treatment of liver cancer.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12920-025-02195-4.

DNA methylation plays a critical role in the dynamics of gene expression regulation and the development of various disorders. Whole-genome bisulfite sequencing can provide single-base resolution of CpG methylation levels and is the “gold standard” for DNA methylation quantification, but its high cost limits its widespread application. In contrast, targeted sequencing provides an optimal, cost-effective solution when focusing on specific candidate regions while providing sufficient sequencing depth. Here, we present a targeted bisulfite sequencing approach in which nanopore sequencing is used to study the methylation status of regions of interest. We applied this workflow to study the promoters of candidate genes associated with severe preterm delivery in a Latin American population. We amplified fragments greater than 1 kilobase in length from 12 genes via long PCR. Each sample was barcoded and pooled for sequencing in MinION flow cells. This approach achieves high sequencing depths, ensuring robust DNA methylation (DNAm) estimates. We detected significant hypomethylation of MIR155HG and hypermethylation of the ANKRD24 gene promoter in severe preterm birth samples, which is concordant with previously reported gene expression changes. This approach represents a scalable and cost-effective method suitable for targeted promoter methylation profiling across several samples. Our study provides a proof-of-concept for larger studies, demonstrating the broad applicability and scalability of our assay to any locus of interest. These features render the method especially apt for clinical diagnostics and precision medicine.

Many early-stage lung adenocarcinoma patients experience recurrence or metastasis after surgery, and the efficacy of targeted therapies remains suboptimal, significantly impacting the prognosis of these patients. Our study aims to investigate the impact of SCGB3A1 on the prognosis of lung adenocarcinoma patients and its role in immunity. We propose that SCGB3A1 may offer a novel treatment approach for lung adenocarcinoma patients who do not respond well to targeted therapies. We obtained RNA sequencing data from 539 lung adenocarcinoma samples, 59 normal tissues, and 2 metastatic cancer tissues from The Cancer Genome Atlas database. Using Venn diagrams, we analyzed the expression of SCGB3A1 and other differentially expressed genes (DEGs) in different patient groups. Additionally, we performed another Venn diagram analysis to explore the association between SCGB3A1 and immune-related genes. We investigated the relationship between SCGB3A1 expression and patient clinical-pathological data and prognosis. Furthermore, through GO, KEGG, and GSEA enrichment analyses, we explored the functional roles of SCGB3A1 and its association with immune cell infiltration and immune checkpoint genes. The role of SCGB3A1 in LUAD was investigated by cytological experiments. The results indicated that SCGB3A1 is associated with both prognosis and immunity. In lung adenocarcinoma, SCGB3A1 may function as a tumor suppressor gene. The high-expression group of SCGB3A1 exhibited a better prognosis and more pronounced immune cell infiltration. Additionally, SCGB3A1 was associated with smoking status and tumor size. A multivariate Cox regression model suggested that SCGB3A1 expression, pathological type, and ethnicity independently impact patient prognosis. Functional enrichment analysis indicated that SCGB3A1 was related to tumor progression, cell proliferation, and immune suppression. Furthermore, ssGSEA analysis revealed that SCGB3A1 expression is associated with immune cell infiltration and tumor-related immune genes. Experimental validation suggested that the overexpression of SCGB3A1 suppressed cell proliferation, migration, and invasion of LUAD. In summary, this study investigated the association between SCGB3A1 and the prognosis of early-stage lung adenocarcinoma. The findings revealed that SCGB3A1 is related to immune cell infiltration and tumor-related immune gene expression, which may provide insights into the role of SCGB3A1 in immunotherapy. The cytological experiments indicate that SCGB3A1 is a potential therapeutic target for LUAD.

PurposeTo investigate chromosomal instability (CIN) in tumor tissue from radical bladder resection and to evaluate whether it can be used as a biomarker for the molecular typing of (BC).MethodsDNA was extracted from formalin-fixed paraffin-embedded samples of 50 BC patients who were followed up to March 23 2023 using the Qiagen nucleic acid kits. We analyzed CIN in tumor of bladder by low-coverage whole genome sequencing (LC-WGS). Kaplan-Meier log-rank test was used to perform survival analysis. The association between variables and overall and progression-free survival was analyzed using the Cox proportional hazards model.ResultsThere were 44 genome segments with statistically significant changes in copy number. CIN was significantly correlated with tumor stage, lymph node metastasis, relapse and survival status. Patients with high CIN were found to have a worse survival, with a median overall survival (OS) of 15 months. In addition, patients with high CIN were more likely to relapse, with a median progression-free survival (PFS) of 7 months. Patients with low CIN showed better OS and PFS. However, there was no significant difference in OS and PFS between T2 and T3-T4 patients. Multivariate cox regression analysis showed that high CIN was an independent predictor of OS, and high CIN and muscle invasion were independent predictors of PFS. Furthermore, patients with abnormal copy number of a single chromosome also had a poor prognosis, with a median survival of 14–30 months for OS and 5–10 months for PFS, while negative patients had a better prognosis.ConclusionCIN was significantly correlated with tumor stage, lymph node metastasis, relapse and survival status of BC. Patients with high CIN or abnormal copy numbers of a single chromosome have a poor prognosis. CIN might be better than T stage in predicting the prognosis of patients with BC. Molecular typing of CIN can be used as an independent prognostic factor for BC.

The risk and prognosis of tuberculosis (TB) are influenced by a complex interplay between human and bacterial genetic factors. While previous genomic studies have largely examined human and bacterial genomes separately, we adopted an integrated approach to uncover host–pathogen interactions. We leveraged paired human and Mycobacterium tuberculosis (M.tb) genomic data from 1000 adult TB patients from Tanzania and used a “genome-to-genome” approach to search for associations between human and M.tb genetic variants and to identify interacting genetic loci. Our analyses revealed two significant host–pathogen genetic associations. The first significant association (p = 4.7e-11) links a human intronic variant in PRDM15 (rs12151990), a gene involved in apoptosis regulation, with an M.tb variant in Rv2348c (I101M), which encodes a T cell-stimulating antigen. The second significant association (p = 6.3e-11) connects a human intergenic variant near TIMM21 and FBXO15 (rs75769176) – also associated with TB severity (p = 0.04) – with an M.tb variant in FixA (T67M). While FBXO15 is involved in the regulation of antigen processing and TIMM21 affects mitochondrial function, FixA's role remains undefined due to limited functional characterization. Additionally, we observed that a group of M.tb T cell epitope variants were significantly associated with HLA-DRB1 variation, suggesting that, despite their rarity, certain epitopes may still be subjected to immune selective pressure. Together, these findings identify previously unknown sites of genomic conflicts between humans and M.tb, advancing our understanding of how this pathogen evades selection pressure and persist in human populations.

Background/PurposeKnowledge of the 3D genome is essential to elucidate genetic mechanisms driving autoimmune diseases. The 3D genome is distinct for each cell type, and it is uncertain whether cell lines faithfully recapitulate the 3D architecture of primary human cells or whether developmental aspects of the pediatric immune system require use of pediatric samples. We undertook a systematic analysis of B cells and B cell lines to compare 3D genomic features encompassing risk loci for juvenile idiopathic arthritis (JIA), systemic lupus (SLE), and type 1 diabetes (T1D).MethodsWe isolated B cells from four healthy individuals, ages 9–17. HiChIP was performed using a CTCF antibody, and CTCF peaks were called within each sample separately. Peaks observed in all four samples were identified. CTCF loops were called within the pediatric samples using three CTCF peak datasets: 1) self-called CTCF consensus peaks called within the pediatric samples, 2) ENCODE’s publicly available GM12878 CTCF ChIP-seq peaks, and 3) ENCODE’s primary B cell CTCF ChIP-seq peaks from two adult females. Differential looping was assessed within the pediatric samples and each of the three peak datasets.ResultsThe number of consensus peaks called in the pediatric samples was similar to that identified in ENCODE’s GM12878 and primary B cell datasets. We observed < 1% of loops that demonstrated significantly differential looping between peaks called within the pediatric samples themselves and when called using ENCODE GM12878 peaks. Significant looping differences were even fewer when comparing loops of the pediatric called peaks to those of the ENCODE primary B cell peaks. When querying loops found in juvenile idiopathic arthritis, type 1 diabetes, or systemic lupus erythematosus risk haplotypes, we observed significant differences in only 2.2%, 1.0%, and 1.3% loops, respectively, when comparing peaks called within the pediatric samples and ENCODE GM12878 dataset. The differences were even less apparent when comparing loops called with the pediatric vs ENCODE adult primary B cell peak datasets.ConclusionThe 3D chromatin architecture in B cells is similar across pediatric, adult, and EBV-transformed cell lines. This conservation of 3D structure includes regions encompassing autoimmune risk haplotypes. Thus, even for pediatric autoimmune diseases, publicly available adult B cell and cell line datasets may be sufficient for assessing effects exerted in the 3D genomic space.

PurposeMicroRNAs(miRNA) play an important role in the pathogenesis of diabetic complications by regulating gene expression. The objective of this paper is to investigate micoRNA expression in diabetic nephropathy (DN), diabetic retinopathy (DR), diabetic neuropathy (DNP), and diabetic cardiopathy (DC). Methods: We conducted this systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement and retrieved eligible microRNA-related studies of diabetic complications from PubMed, Embase, and Web of science databases. We enriched pathways corresponding to differentially expressed miRNAs using the miRPath tool on the DIANA website, and predicted their target genes with DIANA microT-CDS and TargetScan. Results: Although many of the selected studies were of high scientific quality, the results were heterogeneous. Among the 71 selected articles, 79 miRNAs were differentially expressed in various complications of diabetes, of which miRNA126, miRNA192 and 17 others were reported in at least two or more studies. A total of 156 target genes were predicted and 103 pathways were obtained by KEGG enrichment analysis. Conclusion: This comprehensive systematic evaluation provides experimental evidence statistics for miRNAs as circulating biomarkers and highlights promising biomarkers. These results provide preliminary data to further investigate the role of miRNAs in the diagnosis and therapeutic targets of human diabetic complications and support future broader longitudinal studies to better substantiate the role of dysregulated miRNAs as potential biomarkers and therapeutic targets of diabetic complications.