BMC Medical Genomics[JOURNAL]
Sun
200 papers
Association of VDR BsmI polymorphism and vitamin D status with osteoarthritis susceptibility.
Maaruf SM, Mohammad DK, Hassan TS … +7 more , Aziz AD, Yashooa RK, Hassan HT, Agha SSF, Daham RNA, Aali MH, Mustafa SA
BMC Med Genomics · 2026 Mar · PMID 41772562 · Full text
BACKGROUND: Osteoarthritis (OA) is a chronic degenerative joint disease influenced by genetic, environmental, and immunological factors. Vitamin D exerts immunomodulatory and anti-inflammatory effects through the vitamin...
BACKGROUND: Osteoarthritis (OA) is a chronic degenerative joint disease influenced by genetic, environmental, and immunological factors. Vitamin D exerts immunomodulatory and anti-inflammatory effects through the vitamin D receptor (VDR), and genetic variation in the VDR gene may influence susceptibility to OA. However, data from Middle Eastern and Kurdish populations remain limited. OBJECTIVE: This study aimed to evaluate the association between serum vitamin D status and four common VDR gene polymorphisms (FokI, ApaI, TaqI, and BsmI) in Kurdish adults with knee osteoarthritis. METHODS: A hospital-based case-control study was conducted, including 100 OA patients and 100 healthy controls recruited in Erbil, Iraq. Serum vitamin D levels were measured biochemically, and VDR polymorphisms were genotyped using PCR-RFLP and sequencing. Association analyses were performed for polymorphic loci using univariate logistic regression. RESULTS: No allelic or genotypic variation was detected at the FokI (rs2228570), ApaI (rs7975232), or TaqI (rs731236) loci, indicating allele fixation in this population. In contrast, the BsmI (rs1544410) polymorphism exhibited significant variability. The AA genotype was significantly more frequent among OA patients than controls and was associated with increased odds of OA (OR = 2.26, 95% CI = 1.21-4.23; p = 0.006). CONCLUSIONS: The findings indicate that the VDR BsmI polymorphism is associated with knee osteoarthritis in the Kurdish population, whereas FokI, ApaI, and TaqI loci were non-polymorphic. These results highlight population-specific genetic variation within the VDR gene and underscore the need for larger studies incorporating functional validation to clarify the biological relevance of BsmI variation in osteoarthritis.
Single-cell RNA sequencing of adenoid cystic carcinoma of the breast reveals cellular heterogeneity and tumor microenvironment features.
Tang Z, Zhao J, Huang X … +4 more , Liu Q, Wang Y, Zhang C, Li L
BMC Med Genomics · 2026 Feb · PMID 41761191 · Full text
BACKGROUND: Adenoid cystic carcinoma of the breast (ACCB) is a rare malignant tumor with distinct pathological features and a relatively favorable prognosis compared to other breast cancer subtypes, yet its molecular mec...
BACKGROUND: Adenoid cystic carcinoma of the breast (ACCB) is a rare malignant tumor with distinct pathological features and a relatively favorable prognosis compared to other breast cancer subtypes, yet its molecular mechanisms remain poorly understood due to challenges in sample acquisition and targeted research. METHODS: In this study, we employed single-cell RNA sequencing (scRNA-seq) to systematically characterize the cellular heterogeneity and tumor microenvironment in ACCB. We obtained scRNAseq data from a single patient with ACCB and integrated it with publicly available datasets from head and neck adenoid cystic carcinoma (HNACC) and triple-negative breast cancer (TNBC). Through high-resolution gene expression profiling, cell clustering, differential expression analysis, and cell-cell communication analysis, we aimed to identify key malignant subpopulations and regulatory networks in ACCB. RESULTS: Unsupervised clustering revealed seven major cell types in the analyzed ACCB sample, including epithelial cells, fibroblasts, and immune cells. In-depth analysis of epithelial cells identified H19 + myoepithelial cells (H19 + myoEpC) as the dominant malignant subpopulation, enriched in ACCB compared to other cancers and characterized by high expression of oncogenic pathways and ligands such as LAMB1 and WNT6. Tumor-associated fibroblasts exhibited significant heterogeneity, with cancer-associated fibroblasts (CAFs) expressing EMT-related genes and interacting closely with H19 + myoEpC. The tumor microenvironment was immunosuppressive, with reduced infiltration of CD4 + and CD8 + T cells and B cells, and lacked classical Treg/Tex populations. Comprehensive cell-cell communication analysis showed that H19 + myoEpC orchestrated a signaling network with CAFs, immune cells, and endothelial cells, driving tumor progression and immune evasion. CONCLUSIONS: Our study provides the single-cell resolution map of ACCB from a representative case, highlighting the unique role of H19 + myoEpC in tumor progression and immune suppression. These findings offer new insights into the molecular classification of ACCB and potential therapeutic targets.
The functional minisatellite at the 3'-UTR of SLC6A3/DAT1 and dementia spectrum disorders: an association study in a population of Central Italy.
Torbidoni-Baldassari B, Guazzarini AG, Rezza G … +4 more , Bastiani P, Cecchetti R, Mecocci P, Napolioni V
BMC Med Genomics · 2026 Feb · PMID 41761178 · Full text
BACKGROUND: Dementia comprises a spectrum of neurodegenerative disorders marked by progressive cognitive and behavioural decline, with Alzheimer’s disease (AD) being the most prevalent form. While several genetic factors...
BACKGROUND: Dementia comprises a spectrum of neurodegenerative disorders marked by progressive cognitive and behavioural decline, with Alzheimer’s disease (AD) being the most prevalent form. While several genetic factors have been implicated in AD pathogenesis, a significant portion of heritability remains unexplained. One potential contributor to this “missing heritability” is structural variation within non-coding regions, such as variable-number tandem repeats (VNTRs). This study investigated the 40-bp VNTR located in the 3’ untranslated region of the SLC6A3/DAT1 (henceforth referred to as DAT1) gene, a polymorphism previously associated with dopamine regulation and psychiatric conditions, for potential associations with dementia spectrum disorders and related neuropsychiatric phenotypes. METHODS: A cohort of 799 elderly individuals from Central Italy, including AD, mild cognitive impairment (MCI), mixed dementia, and control subjects, was genotyped for the DAT1 VNTR and the APOE alleles. Neuropsychiatric evaluation was performed using the Neuropsychiatric Inventory (NPI). RESULTS: No significant association was observed between DAT1-VNTR genotypes and any dementia diagnosis. However, neuropsychiatric analysis revealed significant associations between DAT1-VNTR genotypes and behavioural symptoms. Carriers of the short (*S) allele showed association with apathy (especially in the presence of APOE*4), irritability, and disinhibition. The *S/*S genotype was notably linked to elevated NPI scores for irritability and disinhibition. CONCLUSIONS: These findings suggest that while the DAT1 VNTR is not directly associated with dementia diagnoses, it may contribute to modulating neuropsychiatric symptoms across dementia types. The results emphasize the importance of investigating non-coding genetic variants and their interactions with established risk alleles, such as APOE*4. Larger studies are needed to validate these findings and explore the functional consequences of DAT1 variation in neurodegeneration. This work contributes to our understanding of the dopaminergic system’s influence on behavioural phenotypes in dementia. It warrants the VNTR as a candidate contributing to neuropsychiatric symptom variability in aging populations.
Short-term exposure of sleep deprivation male model rats to dutasteride promotes the discovery of gene profiles related to fertility impairments.
Zhang S, Li W, Zhang G
BMC Med Genomics · 2026 Feb · PMID 41742262 · Full text
BACKGROUND: Fertility was impaired in sleep deprivation (SD) male rats. Dutasteride (DUT), a 5-α reductase inhibitor, also had negative effects on fertility, however, its definite mechanisms were still unknown. To this e...
BACKGROUND: Fertility was impaired in sleep deprivation (SD) male rats. Dutasteride (DUT), a 5-α reductase inhibitor, also had negative effects on fertility, however, its definite mechanisms were still unknown. To this end, SD male model rats, exposed to DUT for a short period of time, were used to observe whether DUT would exacerbate fertility damage and further to explore the possible mechanism of its fertility damage effects. METHODS: Male rats were randomly divided into 3 groups: Model control (MC) group and the two model groups (i.e. SD group and DUT group). For model groups, the modified multi-platform method was used to model SD for 42 consecutive days. The rats in DUT group were administered by gavage at DUT doses of 20 mg-kg− 1 for 21 consecutive days. Whether the short-term administration of DUT would bring the aforesaid rats about fertility damage was confirmed by observing rats’ behavioral changes, detecting serum testosterone levels, testing sperm-related parameters, and pathological analysis of testicular and epididymal tissue changes. RNA sequencing (RNA-seq) was applied to explore the overall transcriptional profile of genes related to DUT-induced exacerbation of fertility impairment in SD model male rats. By analyzing the differentially expressed genes (DEGs) profiles among those groups, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to explore the gene profile associated with DUT promoting fertility impairments and further to find the mechanism of common fertility damages between SD and DUT. Finally, the transcription of key genes was verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). This experimental work was carried out in 2023–2024. RESULTS: After exposure to DUT, the rats had significantly changed sperm-related parameters and showed further aggravated gonadal tissue damage. Compared with the model control, the SD rats had 445 DEGs. And compared with the SD group, the DUT group had 477 DEGs. Ibsp, Runx1, Fgf18, Areg, Stat6, Mapk3, and Gng4 were screened as the hub genes by Cytohubba. 142 cross-DEGs were identified. Notably, Abca5 expression was continuously decreased in this exposure process. In the cross-DEGs, ABCA5 interacted indirectly with LOR, SLC22A2, PCARE and RCVRN by its family proteins. CONCLUSIONS: Short-term exposure to DUT aggravated the fertility impairment of SD rats and unique actions on the aforesaid hub genes might be one of the possible reasons. The 142 common fertility-impairing DEGs involved in immunological, neurological and metabolic aspects. The abnormal expression of Abca5 and its indirectly associated other cross-DEGs might be the important gene targets for fertility disorders in male rats.
Identification of a novel signature in progression of non-small cell lung cancer based on HdWGCNA and in vitro validation.
Zhang K, Xia W, Li Y … +2 more , Shi B, Yang W
BMC Med Genomics · 2026 Feb · PMID 41742201 · Full text
BACKGROUND: Lung cancer is the predominant contributor to cancer-induced mortality, with non-small cell lung cancer (NSCLC) constituting the majority. However, the intricacies of tumorigenesis and progression in this con...
BACKGROUND: Lung cancer is the predominant contributor to cancer-induced mortality, with non-small cell lung cancer (NSCLC) constituting the majority. However, the intricacies of tumorigenesis and progression in this context remain incompletely understood. METHODS: Utilizing single-cell RNA sequencing data retrieved from the GEO database, we performed high-dimensional weighted gene co-expression network analysis to identify pivotal gene modules exhibiting the highest correlation with the clinical stages of NSCLC patients. Subsequently, we formulated a novel prognostic three-gene signature, subjecting it to thorough analysis using bulk RNA sequencing data obtained from the TCGA-LUAD dataset. RESULTS: A tumor-intrinsic prognostic signature, comprising SEC61G, NPTN, and ALDOA, emerged from our investigation. The risk score derived from this gene signature revealed significantly poorer overall survival among patients in the high-risk group. Patients in different risk groups exhibited distinct immune statuses, with those in the low-risk group likely to benefit more from immunotherapy. Furthermore, in vitro experiments demonstrated that SEC61G facilitates tumor proliferation and migration with the activation of the WNT/β-Catenin signaling pathway. CONCLUSION: Our study unveiled a novel tumor-intrinsic gene signature, shedding light on improved prognostication for NSCLC and facilitating risk-stratified management.
Whole-exome sequencing for the genetic diagnosis of early-onset high myopia and associated hereditary eye disorders.
Han C, Wu S, Yang Y … +2 more , Yang X, Li H
BMC Med Genomics · 2026 Feb · PMID 41742148 · Full text
BACKGROUND: Identification of genetic variations associated with early-onset high myopia (eoHM) provides a genetic basis for risk assessment and prevention of this disease. METHODS: Whole-exome sequencing (WES) was perfo...
BACKGROUND: Identification of genetic variations associated with early-onset high myopia (eoHM) provides a genetic basis for risk assessment and prevention of this disease. METHODS: Whole-exome sequencing (WES) was performed on 41 probands with eoHM with or without other abnormalities. RESULTS: Sixteen high myopia-associated variants identified in 13 probands involved 13 genes comprising 11 autosomal dominant and 2 X-linked genes. The frequency of variants in SNRNP200, ARR3, and COL2A1 was 13%, which was slightly greater than that of other genes. A total of 46% were associated with inherited retinal diseases documented in the RetNet database. According to the relevant guidelines and standards, 9.7%(4/41) of the probands had suspected genetic pathogenic variations through combined clinical-genetic assessment (ID2,3,8,11). Interestingly, we found that the genetic diagnosis rate was significantly correlated with the specific clinical phenotypic characteristics of the patients. The diagnosis rate of patients with ultrahigh myopia was significantly greater than that of patients with high myopia. CONCLUSIONS: Genetic analysis identified the pathogenic factors of many cases of eoHM, revealing a strong association between eoHM candidate genes and hereditary retinal diseases. EoHM is the predominant clinical presentation in most hereditary ocular diseases.
The implementation of Next-Generation Sequencing (NGS) in a Brazilian Public Hospital: a systematic review of challenges and perspectives in oncology.
Elexias SRV, Lopes BA, Acatauassú R … +10 more , Dos Santos LS, Castro T, Chantre-Justino M, Amadeu TP, Carrerette FB, Ornellas MH, Pinto FBR, Loureiro L, Huertas-Vazquez A, Santiago F
BMC Med Genomics · 2026 Feb · PMID 41736042 · Full text
BACKGROUND: Next-generation sequencing (NGS) technology has revolutionized oncology by detecting novel and rare somatic cancer mutations and identifying individuals with pathogenic germline variants, both of which can fa...
BACKGROUND: Next-generation sequencing (NGS) technology has revolutionized oncology by detecting novel and rare somatic cancer mutations and identifying individuals with pathogenic germline variants, both of which can facilitate personalized medicine. By integrating NGS into routine diagnosis in Brazil, patients may benefit from improved treatment responses, however, several barriers to the implementation of NGS in Brazil exist. This review provides practical insights into how NGS can be integrated into diagnostics in public hospitals. METHODS: A comprehensive systematic review was conducted following the guidelines of the Preferred Reporting Items for Systematic Review and Meta Analysis (PRISMA). PubMed, Medline, and Cochrane databases were queried for publications written in English, French, Portuguese, or Spanish from 2014 to February 2025. The research was conducted using Medical Subject Headings (MeSH), including terms such as NGS, public hospital, diagnostic, implementation and Brazilian Public Health System (SUS). RESULTS: Of the 7804 articles identified, 1233 were analyzed with only 10 meeting inclusion criteria. Current literature on NGS is largely centered in the Global North, with limited contributions from low- and middle-income countries. Key challenges included lack of access to molecular profiling and inadequate medical education (27% each), high costs of NGS (23%), data interpretation challenges (15%), and need for additional cost-benefit analyses (8%). Of note, only one paper conducted a cost-effectiveness analysis, demonstrating the utility of NGS in treating cancer. CONCLUSIONS: This systematic review highlights key gaps on NGS implementation in Brazil. There is a need for improved education for healthcare professionals and students to effectively incorporate NGS into clinical oncology practice, as well as strategies to lower costs of sequencing and systematic data interpretation pipelines. Despite these challenges, Brazil has the potential to lead NGS implementation in Latin America. Our experiences at a public hospital may be used as a model to implement NGS through meticulous procurement management, leveraging expertise from basic research, and integrating AI-driven data analysis platforms.
Differentially expressed exosome miRNA profiles as putative prognostic biomarkers for profound sudden sensorineural hearing loss.
Zhang H, Xie H, Cao Q … +5 more , Chen P, Yan S, Zhang X, Gao P, Zhang Y
BMC Med Genomics · 2026 Feb · PMID 41736005 · Full text
BACKGROUND: Sudden sensorineural hearing loss (SSNHL) is an abrupt, often idiopathic hearing decline with uncertain prognosis and multifactorial pathophysiology. Among its subtypes, total deafness—also referred to as pro...
BACKGROUND: Sudden sensorineural hearing loss (SSNHL) is an abrupt, often idiopathic hearing decline with uncertain prognosis and multifactorial pathophysiology. Among its subtypes, total deafness—also referred to as profound SSNHL—carries the worst and most unpredictable prognosis, highlighting an urgent need for reliable biomarkers, especially for prognostic biomarkers. Recent studies have emphasized the potential of exosome microRNAs (miRNAs) as both biomarkers and therapeutic targets in SSNHL, yet very few studies have focused on the profound type. This study aims to preliminarily identify the plasma-derived exosome miRNAs as candidate biomarkers, particularly possible prognostic indicators, in patients with profound SSNHL. METHODS: Of 32 patients with profound SSNHL, six who achieved complete recovery and six age-matched patients with no improvement after two weeks of glucocorticoid therapy were selected for this retrospective study. Six age-matched healthy individuals with normal hearing served as controls. Pretreatment plasma samples were collected, exosomes purified and stored at -80℃. The exosome samples from 18 enrolled participants were subjected to RNA extraction and small RNA sequencing. Differentially expressed exosome miRNAs (DEEMs) were identified using the DESeq R package, with significance thresholds set at p < 0.05 and |log₂(fold change)| > 1. Predicted target mRNAs of DEEMs between the recovery and no improvement groups were analyzed for pathway enrichment using the Metascape database. RESULTS: We identified 12 candidate DEEMs (10 downregulated and 2 upregulated) shared across all profound SSNHL groups compared to healthy controls, and 14 candidate DEEMs (6 downregulated and 8 upregulated) between the no improvement group and the recovery group. The six pronounced changed miRNAs out of those 14 were hsa-miR-320d, hsa-miR-146a-3p, hsa-miR-132-3p, hsa-miR-9-3p, hsa-miR-219b-5p, and hsa-miR-219a-2-3p. The target mRNAs of these top six miRNAs were mainly enriched in pathways of embryonic development, tube morphogenesis, cell division, synaptic transmission, STAT3 and TGF-β signaling, autophagy, cellular import, ketone response, and cellular responses to interleukin-1 and stress. CONCLUSIONS: By exosomal miRNA profiling from patients of different treatment outcomes,, this exploratory study initially identified potential DEEMs that may serve as candidate biomarkers for profound SSNHL, although larger, independently replicated studies are required.
Diagnostic value of karyotyping, CMA/CNV-seq, and WES in fetuses with thickened nuchal translucency: perinatal and two-year follow-up outcomes.
Wang M, Ji Y, Xu Y … +4 more , Sun S, Yang X, Sun L, Wu Q
BMC Med Genomics · 2026 Feb · PMID 41723443 · Full text
BACKGROUND: This study aimed to analyze the perinatal and pediatric outcomes of fetuses with thickened nuchal translucency (NT ≥ 2.5 mm) to enhance prenatal diagnostic strategies. STUDY DESIGN: A total of 720 pregnant wo...
BACKGROUND: This study aimed to analyze the perinatal and pediatric outcomes of fetuses with thickened nuchal translucency (NT ≥ 2.5 mm) to enhance prenatal diagnostic strategies. STUDY DESIGN: A total of 720 pregnant women with NT ≥ 2.5 mm in the first trimester underwent interventional prenatal diagnosis. These participants were followed up during the perinatal and pediatric periods (2 years after birth). RESULTS: The detection rate of fetal chromosomal karyotype abnormalities was 32.86%, with trisomy 21 being the most common abnormality. Chromosomal microarray analysis (CMA) and copy number variation sequencing (CNV-seq) increased the detection rate by 10.72%. The most prevalent pathogenic copy number variations (pCNVs) and likely pathogenic copy number variations (lpCNVs) were associated with 22q11.21 microdeletion/duplication syndrome and 15q11.2 microdeletion syndrome, respectively. Excluding pathogenic karyotype abnormalities and pCNV/lpCNVs, the rate of pathological deformities was 19.6%. Whole-exome sequencing (WES) was performed in 11 cases, yielding a detection rate of 72.7% (8/11). There were 339 pregnancy terminations and 381 live births, of which 337 had normal karyotypes, CNVs, and ultrasound results, resulting in a live-birth detection rate of 96.8%. In addition, two cases of psychomotor retardation were identified. CONCLUSION: Traditional karyotyping, CMA/CNV-seq testing, and detailed ultrasound examinations are vital diagnostic tools that support genetic counseling for fetuses with thickened NT in the first trimester. Therefore, novel and efficient WES testing is required.
Hub genes and molecular mechanisms related to hypospadias based on transcriptome sequencing data and bioinformatics analysis.
Yao H, Fan Y, Li L … +3 more , Zhang S, Du K, Yue J
BMC Med Genomics · 2026 Feb · PMID 41721400 · Full text
BACKGROUND: Hypospadias, a prevalent congenital anomaly affecting patients’ quality of life, remains incompletely understood in terms of its pathogenesis. This study aimed to identify key genes and molecular mechanisms t...
BACKGROUND: Hypospadias, a prevalent congenital anomaly affecting patients’ quality of life, remains incompletely understood in terms of its pathogenesis. This study aimed to identify key genes and molecular mechanisms through transcriptome sequencing and bioinformatics analysis. METHODS: Transcriptome sequencing was conducted on foreskin samples from 15 patients with hypospadias and 15 controls. Differential expression analysis and WGCNA were used to identify differentially expressed genes (DEGs) and key modules. Genes common to both approaches were further analyzed through PPI network filtering, followed by feature selection using LASSO and SVM-RFE algorithms. Hub genes were identified based on an AUC > 0.8. Functional, immune, and regulatory analyses were performed to investigate their biological roles. RESULTS: Three hub genes—CSF3R, SELL, and FCN1—demonstrated significant diagnostic potential (AUC > 0.8). Functional enrichment analysis revealed their association with cytokine receptor interaction and chemokine signaling pathways. Eleven immune cell types, including activated dendritic cells, were found to be elevated in the patient cohort. All hub genes were upregulated in the disease group. CONCLUSION: CSF3R, SELL, and FCN1 represent potential diagnostic biomarkers for hypospadias and provide valuable insights into its molecular mechanisms and potential therapeutic approaches.
A novel inversion at 17q12 disrupting HNF1B gene in a patient with renal cysts and diabetes syndrome.
Wang Y, Wang Q, Guan L … +6 more , Jiang T, Wang D, Wu R, Gu C, Wang D, Zhu Y
BMC Med Genomics · 2026 Feb · PMID 41703530 · Full text
BACKGROUND AND OBJECTIVE: This study aims to elucidate the genetic cause of polycystic kidney disease detected in the proband during the fetal period and progressively worsening, thereby providing a reference for researc...
BACKGROUND AND OBJECTIVE: This study aims to elucidate the genetic cause of polycystic kidney disease detected in the proband during the fetal period and progressively worsening, thereby providing a reference for research on pediatric polycystic kidney disease. METHODS: Whole-genome sequencing was performed on the proband and family members to identify pathogenic variants. The candidate variants were validated by Sanger sequencing. Finally, bioinformatics analysis tools were employed to predict and evaluate the pathogenicity. RESULTS: A previously unreported, de novo chromosomal inversion(GRCh38:17:g.36934029_37729559inv) was identified in the proband. This variant disrupts the HNF1B gene structure and causes Renal Cysts and Diabetes Syndrome (RCAD). DISCUSSION: Our study identifies (GRCh38:17:g.36934029_37729559inv) in HNF1B as a pathogenic variant underlying RCAD through gene disruption, expanding its known pathogenic variant spectrum. It highlights the value of whole-genome sequencing in detecting complex structural variants and provides crucial evidence for genetic counseling.
Genetic insights into hepatocellular carcinoma: the role of VDR FokI (rs2228570) and TaqI (rs731236) polymorphisms in Egyptian patients.
Alrdahe SS, Darwish DBE, Albalawi AE … +4 more , Omran AME, Almasaudi NM, Elsaid AM, Youssef MM
BMC Med Genomics · 2026 Feb · PMID 41668036 · Full text
BACKGROUND: Hepatocellular carcinoma (HCC) is the most dominant form of cancer. Its development is influenced by environmental exposures, lifestyle factors, and genetic predispositions. Beyond its classical function in s...
BACKGROUND: Hepatocellular carcinoma (HCC) is the most dominant form of cancer. Its development is influenced by environmental exposures, lifestyle factors, and genetic predispositions. Beyond its classical function in skeleton and mineral metabolism, vitamin D also plays critical roles in immune regulation, tissue fibrosis, and tumor progression through interaction with the vitamin D receptor (VDR). This study aimed to investigate whether variants in the VDR gene are associated with HCC risk in an Egyptian cohort. METHODS: One hundred HCC cases were recruited along with 100 age- and sex-matched healthy controls. Genotyping of the VDR FokI (rs2228570) and TaqI (rs731236) polymorphisms was performed by means of ARMS-PCR assay. RESULTS: The VDR FokI (rs2228570 f-allele) and TaqI (rs731236 t-allele) were detected at significantly higher frequencies among HCC patients than healthy participants, and both were associated with increased disease risk (p = 0.002 and p = 0.006, respectively). CONCLUSION: The results indicate that those variants in the VDR FokI and TaqI genes may increase the predisposition to hepatocellular carcinoma among Egyptians.
Clinically actionable pharmacogenomic variants for anticancer therapy in Nigeria: first comprehensive variant profiling in underrepresented Nigerian cohorts.
Ukpe MP, Ezeanuka AC
BMC Med Genomics · 2026 Feb · PMID 41664142 · Full text
BACKGROUND: Advances in pharmacogenomic research have ushered in a new era of precision medicine in cancer care. However, evidence on the effects of pharmacogenomic variants on anticancer drug efficacy and safety in the...
BACKGROUND: Advances in pharmacogenomic research have ushered in a new era of precision medicine in cancer care. However, evidence on the effects of pharmacogenomic variants on anticancer drug efficacy and safety in the Nigerian population is scarce. As a result, pharmacogenomic testing is not currently included in cancer care in Nigeria. This study aimed to investigate the minor allele frequencies (MAFs) and genotype distributions of all clinically validated pharmacogenomic variants associated with anticancer drugs in the Nigerian population at PharmGKB Level A1. METHODS: Allele counts and allele frequencies of germline pharmacogenomic variants associated with cancer therapeutics obtained from the Clinical Pharmacogenetics (ClinPGx) database were retrieved from the Phase 3 1,000 Genomes project via the Ensembl REST API and genome browser. The primary population of interest in this study was the 207 Nigerians included in the 1000 Genomes Project (1KGP) (the Yoruba (n = 108) and Esan (n = 99) tribes). The study included pharmacogenetic variants with Level 1 A evidence CYP2D6*4 (Tamoxifen), CYP3A5*3, *6, *7 (Tacrolimus), DPYD rs115232898, rs17376848, rs1801159, rs1801265 (5-Fluorouracil and Capecitabine), and TPMT*3C (Thiopurines: 6-MP, Azathioprine). Hardy–Weinberg equilibrium (HWE) was calculated, and a cross-population comparative analysis was conducted between Nigerian populations and global reference populations from Europe (British), East Asia (Han Chinese), and the Americas (Peruvians). RESULTS: Among the Esan and Yoruba populations in Nigeria, CYP2D6 poor metabolizer phenotypes (defined by two non-functional diplotypes according to CPIC) were infrequent and observed for CYP2D6*4 at a frequency of 1.0% (95% CI: 0.2–5.5) in the Esan population, while absent in the Yoruba population, with potential implications for reduced tamoxifen efficacy. Homozygosity for non-functional CYP3A5 alleles (*3, *6, and 7), indicating complete loss of CYP3A5 expression and corresponding to poor tacrolimus metabolizer status, was identified in approximately 3% of the Esan population and nearly twice that proportion in the Yoruba population. The minor allele frequency of DPYD rs115232898, associated with decreased fluorouracil metabolism, differed between populations, occurring at 1.0% (95% CI: 0.3–3.6) in Esan and 4.2% (95% CI: 2.2–7.7) in Yoruba individuals. For TPMT*3C, non-functional diplotypes were not observed in the Esan population, whereas a low frequency (0.9%) was detected among Yoruba individuals. Global comparisons showed marked population specificity: CYP3A5*6 and *7 nonfunctional alleles were enriched in Nigerians compared to British, Peruvians and Han Chinese populations. The decreased function DPYD rs115232898 allele was observed at a frequency of 3% among Nigerians and was absent in all 3 global populations examined. Within Nigeria, its frequency was approximately 4 times higher in the Yoruba population (Esan: 1%, Yoruba: 4%). CONCLUSION: These population-specific patterns highlight the clinical importance of pharmacogenetic screening to guide dose optimisation and improve cancer treatment outcomes. Integrating pharmacogenomic testing into oncological care in Nigeria would enhance therapeutic efficacy, minimise adverse effects, and advance the implementation of precision medicine across African populations.
A novel EVC2 splice-site variant expands the mutational and phenotypic spectrum of Weyers acrofacial dysostosis.
Chen A, Zhang W, Long P … +8 more , Chen X, Zhang A, Zhu H, Zeng L, Xiong F, Wang J, Zhu S, Zhou P
BMC Med Genomics · 2026 Feb · PMID 41664038 · Full text
BACKGROUND: Weyers acrofacial dysostosis (WAD) is a rare autosomal dominant ciliopathy caused by heterozygous pathogenic variants in the EVC2 gene. The classic phenotype includes short stature, dental anomalies, and nail...
BACKGROUND: Weyers acrofacial dysostosis (WAD) is a rare autosomal dominant ciliopathy caused by heterozygous pathogenic variants in the EVC2 gene. The classic phenotype includes short stature, dental anomalies, and nail dysplasia. To date, all reported causative variants are truncating mutations located within the last exon (exon 22). In contrast, pathogenic variants in other regions, particularly splice-site variants, remain poorly characterized. The co-occurrence of WAD and epilepsy has rarely been documented. METHODS: We performed exome sequencing in a proband with comorbid developmental and epileptic encephalopathy (DEE) and WAD features. A candidate splice-site variant was further investigated using an in vitro minigene splicing assay. RESULTS: Exome sequencing identified a de novo heterozygous splice-site variant in EVC2 (c.451-1G > T). Minigene analysis confirmed that this variant causes complete skipping of exon 4, predicted to lead to an in-frame deletion (p.Tyr151_Leu173del). To our knowledge, this is the first report of a pathogenic splice-site variant in this region of EVC2 associated with WAD and DEE. CONCLUSION: Our study expands the mutational spectrum of EVC2. It underscores the utility of exome sequencing coupled with functional assays for diagnosing complex cases.
Genome-wide profiling of salivary promoter-region DNA methylation in periodontitis: the Tromsø Study.
Petrenya N, Jönsson B, Hadler-Olsen E … +6 more , Larsson L, Flatberg A, Beisvåg V, Holde GE, Zykova SN, Asa'ad F
BMC Med Genomics · 2026 Feb · PMID 41652412 · Full text
BACKGROUND: Methylation of DNA is an epigenetic reversible process that regulates gene expression. Aberrant promoter methylation is associated with chronic inflammation; however, the genome-wide DNA promoter methylation...
BACKGROUND: Methylation of DNA is an epigenetic reversible process that regulates gene expression. Aberrant promoter methylation is associated with chronic inflammation; however, the genome-wide DNA promoter methylation signature in periodontitis remains unexplored. METHODS: The present study is an epigenome-wide association study (EWAS) aimed at investigating salivary DNA methylation patterns within gene promoter regions in individuals with Stage III/IV periodontitis compared to healthy controls. Cases (all available individuals with Stage III/IV and probing pocket depths (PPD) > 5 mm, n = 50, 48% women) were participants in an oral health examination (40–54-year-old subsample, n = 1668) of the population-based seventh survey of the Tromsø Study, conducted from 2015 to 2016. Periodontally healthy controls with similar age and sex to the cases (n = 50, 58% women) were randomly selected from the same subsample. We used the Illumina DNA methylation BeadChip technology, targeting ~ 935 K unique methylation sites. The R package RnBeads was used to study the difference in methylation. Separate lists of all significantly (comb.p.adj.fdr < 0.05) hypomethylated (hypoMPs, n = 3411) and hypermethylated (hyperMPs, n = 3437) promoters in participants with periodontitis relative to controls were used as inputs for enrichment analysis (g:Profiler) and network visualization (Cystoscape). RESULTS: Gene ontology terms enriched among the hypoMPs included DNA biosynthesis, cell cycle/checkpoint, nuclear chromosome, endoplasmic reticulum, regulation of inflammatory response and leucocyte activation, cell adhesion, TRIF-dependent Toll-like receptor signaling, tyrosine phosphorylation of STAT proteins, regulation of PI3K/Akt, collagen extracellular matrix, and mucopolysaccharide metabolic process. HyperMPs were enriched in mRNA catabolism, mitochondrial electron transport, intrinsic apoptotic signaling, B-lymphocyte differentiation, actin cytoskeleton, regulation of extracellular matrix organization, epithelial-mesenchymal transition, ubiquitination, wound healing, acylglycerol metabolism, and serine/threonine signaling. NF-κB, GMEB-1, and IRF-8 were enriched in hypoMPs; ZFP85, ELF-5, and HNF4-alpha in hyperMPs. CONCLUSIONS: We identified a differential DNA promoter methylation signature in participants with Stage III/IV periodontitis in middle adulthood. Our study highlights biological pathways involved in inflammation, immune response, tissue destruction, and repair that may be epigenetically dysregulated.
Successful experience with high-risk and family screening for Fabry disease in Ninghai County, Zhejiang Province, Eastern China: genotype‒phenotype analysis of the GLA IVS4 + 919G > A variant.
Ge Z, Mao J, Dai Z … +9 more , Pan X, Lin K, Lu Z, Yang M, Lai T, Zhang H, Gong H, Li G, Hu Z
BMC Med Genomics · 2026 Feb · PMID 41645213 · Full text
BACKGROUND: Fabry disease is a rare and non-specific disease that is difficult and expensive to diagnose. This study aimed to investigate the clinical phenotypes and genetic characteristics of patients with Fabry disease...
BACKGROUND: Fabry disease is a rare and non-specific disease that is difficult and expensive to diagnose. This study aimed to investigate the clinical phenotypes and genetic characteristics of patients with Fabry disease characterised by the GLA IVS4 + 919G > A variant in China through a proposed pilot program integrating high-risk and family screening. METHODS: The 31-months-long pilot program assessed high-risk screening for Fabry disease in 388 patients by integrating previous screening methods that measure their dry blood spot (DBS) α-galactosidase A (α-GAL) activity, globotriaosylsphingosine (Lyso-GL-3), and GLA gene sequence at Ninghai First Hospital. Patients whose dried blood spot (DBS) α-GAL enzyme activity was low (< 2.40 µmol·L− 1·h− 1) or whose Lyso-GL-3 level was high (> 1.10 ng/mL) underwent GLA genetic testing for diagnostic confirmation. Gender-specific family screening and evaluation was carried out on the proband, and the clinical and genetic characteristics of Fabry disease characterised by the GLA IVS4 + 919G > A variant were summarised. RESULTS: A yield of Fabry disease diagnosis of 1.80% (7/388) was achieved, which is much larger than have been previously reported. These diagnoses include a 9.8-year-old girl, who was screened because of a high-risk profile of severe pain in the extremities, as well as 6 males, who were diagnosed with Fabry disease and who were screened because of unexplained left ventricular hypertrophy. All 7 diagnosed patients were carriers of the GLA IVS4 + 919G > A variant. Family screening of 7 probands revealed that 18 family members carried pathogenic variants, resulting in a diagnosis rate of 6.44% (25/388); 13 were clinically affected, 2 were asymptomatic carriers, and 3 declined further clinical assessment. The 25 patients had multiple affected organs and systems included the heart (60.00%), peripheral nerves (16.00%), kidney (36.00%), eye (20.00%), brain (12.00%), and gastrointestinal tract (24.00%). CONCLUSIONS: Screening high-risk populations and family screening is critical for early diagnosis and timely intervention in patients with Fabry disease. The GLA IVS4 + 919G > A variant is associated with diverse phenotypes of Fabry disease and is highly prevalent in late-onset cases in Ninghai County, Zhejiang Province, Eastern China.
A novel homozygous ADAMTS10 frameshift variant in Weill-Marchesani syndrome in a Chinese family.
Li M, Bai R, Lian Y … +3 more , Shu C, Li H, Sheng X
BMC Med Genomics · 2026 Feb · PMID 41639873 · Full text
BACKGROUND: Weill–Marchesani syndrome (WMS) is a rare connective tissue disorder. The main clinical features include short stature with a stocky build, brachydactyly, joint stiffness, and microspherophakia. The syndrome...
BACKGROUND: Weill–Marchesani syndrome (WMS) is a rare connective tissue disorder. The main clinical features include short stature with a stocky build, brachydactyly, joint stiffness, and microspherophakia. The syndrome can be inherited in an autosomal dominant manner due to heterozygous pathogenic variants in FBN1, as well as in an autosomal recessive manner associated with biallelic pathogenic variants in ADAMTS10, ADAMTS17, or LTBP2. Despite differences in inheritance patterns, the clinical manifestations are consistent. Therefore, clinical diagnosis requires genetic testing of the proband to determine the genotype, confirm the diagnosis. METHODS: This study collected blood samples from a child with Weill–Marchesani syndrome (WMS) and their family members from a Chinese family. Comprehensive ophthalmologic and systemic examinations were performed. Whole-exome sequencing (WES) was conducted to detect genetic variants, and bioinformatics tools were used to screen for potential pathogenic variants. Suspected variants were validated by Sanger sequencing and comprehensively evaluated in combination with clinical data. Using the keywords “ADAMTS10” and “Weill–Marchesani syndrome,” relevant cases were retrieved from databases such as PubMed, CNKI (China National Knowledge Infrastructure), and Wanfang Medical. The genotypes and clinical manifestations of reported cases were analyzed and summarized. RESULTS: The proband presented with clinical features including short stature, brachydactyly, and ocular abnormalities. Ocular manifestations included high myopia, microspherophakia, and glaucoma. Whole-exome sequencing revealed a homozygous frameshift duplication variant in the ADAMTS10: NM_030957.4:c.1560_1575dup; p.Ile526Valfs*51. Both phenotypically normal parents were heterozygous carriers of the same variant. According to the variant interpretation principles of the Human Gene Mutation Database (HGMD) and the guidelines of the American College of Medical Genetics and Genomics (ACMG), this variant was classified as pathogenic. A review of the literature indicated that WMS associated with ADAMTS10 variants exhibits complex and heterogeneous clinical phenotypes. CONCLUSION: A novel homozygous frameshift variant of ADAMTS10is identified in a WMS family with a history of consanguineous marriage. Our study expands the range of variations associated with WMS and deepens our understanding of pathology in disease associated with ADAMTS10 variants.
DMBX1 expression in colon cancer and its impact on prognosis and the tumor microenvironment.
Zhang K, Hu X, Chen J … +4 more , Zhao Z, Yin X, Zhou L, Wang B
BMC Med Genomics · 2026 Feb · PMID 41634710 · Full text
BACKGROUND: DMBX1 is a transcription factor that plays important roles in various biological processes. However, systematic research on DMBX1 in colon cancer remains limited. This study aimed to investigate the expressio...
BACKGROUND: DMBX1 is a transcription factor that plays important roles in various biological processes. However, systematic research on DMBX1 in colon cancer remains limited. This study aimed to investigate the expression characteristics of DMBX1 in colon cancer and its impact on prognosis and the immune microenvironment. METHODS: Gene expression and clinical data for colon cancer were downloaded from The Cancer Genome Atlas (TCGA) database. Analyses performed included differential gene expression analysis, mutation analysis, prognosis analysis, tumor microenvironment (TME) analysis (including immune cell infiltration, immune checkpoints, DNA repair genes, and methyltransferase correlation analysis), and functional enrichment analysis. Furthermore, the function of DMBX1 was validated through Western blot, Transwell, and cell scratch assays, including knockdown and overexpression of DMBX1. RESULTS: Differential expression analysis revealed that DMBX1 expression was significantly higher in colon cancer tissues compared to normal tissues. Its high expression was significantly associated with poorer patient survival (p < 0.05). Mutation analysis found that the DMBX1 gene has a relatively high mutation frequency in colon cancer, and different mutation types significantly affected its gene expression levels. Tumor microenvironment analysis indicated that DMBX1 gene expression was significantly correlated with the infiltration levels of various immune cells and the expression of immune checkpoint genes. Enrichment analysis results showed that DMBX1 is involved in multiple key biological processes and signaling pathways, particularly participating in the process of cell adhesion. After knocking down the DMBX1 gene, the expression of ZO-1 and E-cadherin increased, while the expression of Vimentin and Slug decreased, suggesting that DMBX1 may affect the invasion and metastasis of colon cancer by regulating the epithelial-mesenchymal transition (EMT) process. Conversely, overexpression of DMBX1 led to decreased expression of ZO-1 and E-cadherin and increased expression of Vimentin and Slug. Transwell and cell scratch assay results further validated that high expression of DMBX1 significantly increased the invasion and migration capabilities of colon cancer cells, while knocking down DMBX1 inhibited these capabilities. CONCLUSION: Our findings suggest that DMBX1 may have potential as a prognostic biomarker for prognostic assessment in colon cancer and is associated with alterations in the tumor immune microenvironment.Mechanistically, DMBX1 likely primarily influences the occurrence and development of colon cancer by promoting the invasion and migration of colon cancer cells.
Cardiovascular-kidney-metabolic syndrome: candidate subtypes and genetic risk factors.
Donker HC, Bisht V, Dwivedi OP … +4 more , Mueller S, Neijzen D, Ding Z, Lunter G
BMC Med Genomics · 2026 Jan · PMID 41620767 · Full text
BACKGROUND: Cardiovascular-kidney-metabolic (CKM) syndrome is increasingly recognized as a distinct disorder with important implications for health outcomes, but its heterogeneity of presentation and genetic underpinning...
BACKGROUND: Cardiovascular-kidney-metabolic (CKM) syndrome is increasingly recognized as a distinct disorder with important implications for health outcomes, but its heterogeneity of presentation and genetic underpinning remains poorly understood. We aimed to identify potential CKM subtypes and their genetic basis by analyzing biomarkers and health outcomes in a large biobank. METHODS: Blood and urine biomarkers from 121,918 participants in the Lifelines cohort were analyzed using topic modelling. Candidate CKM subtypes were operationally defined as blood-urine topics that were simultaneously and positively associated with self-reported kidney disease, type 2 diabetes, and cardiovascular disease. Genome-wide association studies were performed on 52,727 genotyped participants to identify common genetic variants linked to these candidate subtypes. RESULTS: Five candidate CKM subtypes were identified, each characterized by high levels of blood glucose, uric acid, urea and inflammation biomarkers, but differing in liver enzyme, cholesterol, and glycaemic profiles. Genetic analyses revealed 57 genome-wide significant variants, with the majority (35) not detected in single-biomarker analyses. Most variants were subtype-specific, suggesting that distinct biological pathways contribute to these candidate CKM subtypes. CONCLUSIONS: Our analysis suggests distinct genetic architectures underlying different CKM manifestations and demonstrates that combining biomarkers in disease-relevant constellations improves detection of genetic variants.
Designing inclusive newborn sequencing research: insights from parents in underrepresented communities.
Del Rosario MC, Walmsley SA, Harrison BW … +19 more , Stephens CT, Zettler B, Rivera-Cruz G, Agrawal P, Brower A, Chigbu S, Christensen KD, Genetti CA, Givens R, Gold NB, Reeves IV, Schichter I, Shariat H, Simon S, Smith HS, Uveges M, Green RC, Holm IA, Pereira S
BMC Med Genomics · 2026 Jan · PMID 41593648 · Full text
BACKGROUND: It is essential that studies of genomic sequencing (GS) in newborns and children include individuals from under-represented racial and ethnic groups (URG) to ensure future applications are equitably implement...
BACKGROUND: It is essential that studies of genomic sequencing (GS) in newborns and children include individuals from under-represented racial and ethnic groups (URG) to ensure future applications are equitably implemented. We conducted interviews with parents from URG to better understand their perspectives on GS research, develop strategies to reduce barriers to enrollment, and facilitate research participation. METHODS: Semi-structured interviews with 50 parents from URG. RESULTS: Nearly all parents said they would be interested in participating in an infant GS study. Parents were interested in participating in GS research for reasons including clinical utility, personal utility, and/or family health benefits. Deterrents to enrollment cited by parents were discomfort with enrollment procedures (e.g., not wanting a heel stick), limited emotional bandwidth, unfavorable perceptions of the study, and concerns about potential results. Most parents said they would want to receive all types of genetic results, including actionable and non-actionable, as well as childhood- and adult-onset. CONCLUSION: Our findings demonstrate that parents from URG are interested in participating in GS research. Based upon these findings, we provide recommendations for designing GS studies that are responsive to their concerns.
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