Prenatal RhD screening enables risk stratification for RhD-associated hemolytic disease of the fetus and newborn (HDFN) and supports rational，evidence-based use of prophylactic anti-RhD immunoglobulin. However, noninvasive prenatal RhD screening remains challenging in the Chinese population, primarily due to population-specific RHD allelic diversity and the limited adaptability of current assay designs. We developed and optimized a real-time PCR–based assay for noninvasive prenatal RHD genotyping, specifically designed to accommodate the spectrum of clinically relevant RHD alleles in the Chinese population. By simultaneously targeting RHD exons 5, 9, and 10, the assay enables detection of paternally inherited RHD alleles within a single analytical workflow. This assay facilitates accurate fetal RHD status determination in pregnancies involving the predominant RhD-negative alleles, including RHD*01N.01, RHD*01N.03, and RHD*01EL.01. The assay accurately predicted fetal RHD status across all simulated maternal genotypes, including those carrying non-deletion alleles such as RHD*01N.03 and RHD*01EL.01. This study presents a methodological framework for noninvasive prenatal RHD genotyping, specifically optimized for Chinese and other East Asian populations. Assay performance relies on distinct amplification patterns of population-specific RHD alleles across exons 5, 9, and 10. In addition, inclusion of exon 5 allows detection of RHD variants frequently observed in African populations, suggesting potential applicability across genetically diverse populations, pending further population-specific validation.
Imagawa-Matsumoto syndrome (IMMAS) is a rare overgrowth disorder caused by heterozygous loss-of-function variants in SUZ12, which encodes a core subunit of the Polycomb Repressive Complex 2 (PRC2). To date, fewer than 20 cases have been reported, and the molecular mechanisms underlying PRC2 dysfunction in IMMAS remain incompletely understood. Trio-based whole-exome sequencing (Trio-WES) was performed in a Chinese family presenting with overgrowth and dysmorphic features. The candidate variant was validated by Sanger sequencing and segregation analysis. AlphaFold 3 was used to predict the structural consequences of the variant. In vitro overexpression and protein assays were conducted to evaluate SUZ12 protein expression and subcellular localization. The proband exhibited global developmental delay, macrocephaly, hypertrichosis, and distinctive craniofacial dysmorphism. Trio-WES identified a heterozygous frameshift variant in SUZ12 (c.1244_1248del; p.Glu415GlyfsTer5). Computational modeling predicted that the truncating variant removes the ZnF and VEFS domains and may affect the predicted SUZ12–EZH2 interface. In vitro expression of the mutant construct confirmed the production of a truncated SUZ12 protein. Furthermore, peripheral blood mononuclear cells (PBMCs) from both the proband and her mother showed a substantial global reduction in H3K27me3 levels, consistent with impaired PRC2-mediated histone methylation in vivo. We report a Chinese family with Imagawa-Matsumoto syndrome harboring a SUZ12 frameshift variant (c.1244_1248del; p.Glu415GlyfsTer5). Our study expands the phenotypic spectrum associated with this variant and provides evidence consistent with impaired PRC2-mediated histone methylation.
Long QT syndrome (LQTS) is considered a primary cardiac ion channelopathy. Several studies have shown that myocardial functional alterations may occur in patients with LQTS type 3 (LQT3). However, it is currently unclear whether there is a specific relationship between phenotype and genotype. The aim of this study is to provide additional information on the phenotype and genotype of LQT3 caused by a novel delKKP 1504–1506 mutation in a Chinese family. The family came to our attention because of a sustained corrected QT interval (QTc) prolongation in a 14-year-old girl who had experienced a loss of consciousness with Mobitz type II atrioventricular block one year earlier. Three family members carrying the delKKP 1504–1506 mutation demonstrated a combination of infero-apical left ventricular aneurysms and prolonged QTc, and two members showed J-waves in the right precordial lead V2. This case suggests that the delKKP 1504–1506 mutation in SCN5A may not only lead to impaired impulse propagation in the conduction system and a prolonged QTc, but may also be associated with infero-apical ventricular aneurysms and J-wave syndromes, possibly corresponding to regional myocardial fibrosis.
Craniosynostosis is a genetically heterogeneous craniofacial disorder caused by the premature fusion of one or more cranial sutures. Pathogenic variants in TCF12, encoding a basic helix–loop–helix (bHLH) transcription factor, represent a major cause of autosomal dominant coronal craniosynostosis and are characterized by incomplete penetrance and marked phenotypic variability. However, clinical and molecular data from Asian pediatric populations remain limited. Trio-based whole-exome sequencing was performed on ten pediatric patients with cranial deformities and their parents. The identified TCF12 variants were classified according to the American College of Medical Genetics and Genomics (ACMG) guidelines and validated by Sanger sequencing. Detailed clinical and radiological data were collected. In addition, a comprehensive literature review was conducted to summarize previously reported TCF12 variants and associated phenotypes. Ten distinct heterozygous TCF12 variants were identified in ten unrelated pediatric patients, all of which were classified as pathogenic or likely pathogenic according to ACMG criteria. Six variants were inherited, and four occurred de novo. Seven patients had imaging-confirmed craniosynostosis, predominantly involving the coronal sutures (five bilateral and one unilateral), while one patient presented with multisuture craniosynostosis (left coronal and sagittal sutures). Three patients showed cranial deformities without radiographic evidence of suture fusion. Phenotypic heterogeneity and incomplete penetrance were observed, including a mildly affected parent. Most pathogenic variants were truncating variants distributed mainly across exons 14–19 and predicted to induce loss of function, either through nonsense-mediated mRNA decay or the production of truncated proteins lacking the entire C-terminal bHLH domain. Structural modeling analysis further indicated that the bHLH-domain-located missense variant p.Arg603Trp alters the local DNA-binding conformation of TCF12 and impairs its binding affinity to the E-box DNA motif. This study provides additional clinical and molecular data on TCF12-related craniosynostosis in a pediatric cohort from an Asian population. Our findings support haploinsufficiency as the central pathogenic mechanism, primarily driven by truncating variants affecting the C-terminal bHLH domain. The marked clinical heterogeneity, the presence of mild or evolving phenotypes, and incomplete penetrance observed in our cohort underscore the importance of early diagnosis and longitudinal clinical surveillance in affected families.
Autism spectrum disorder (ASD) is a neurodevelopmental condition including incorrect functioning in communication, social interaction, and repetitive behavior. Global prevalence is estimated as 1–2
The PTPN22 gene encodes Lyp, a phosphatase involved in downregulating T-cell receptor signaling and modulating immune homeostasis. Although PTPN22 polymorphisms rs2476601 (R620W) and rs33996649 (R263Q) are associated with autoimmune diseases, their role in infectious diseases such as tuberculosis susceptibility remains unclear. To evaluate the association of PTPN22 polymorphisms with TB susceptibility and assess their functional relevance through gene expression profiling in a South Asian cohort. PTPN22 polymorphisms and expression in 111 TB patients and 85 controls were analyzed by ARMS-PCR and RT-qPCR, with association and predictive analyses performed using logistic regression, ROC, LD (Haploview), and SPSS v26. A significant association was observed between the rs33996649 C/T genotype and increased TB susceptibility (p < 0.008; OR = 5.87), while no significant association was found for rs2476601. Logistic regression indicating a stronger contribution to TB risk for rs33996649 (1.1279) compared to rs2476601 (0.2276). ROC curve analysis yielded an area under the curve (AUC) of 0.63, suggesting good predictive power for the combined genetic model. Linkage disequilibrium analysis demonstrated low correlation between the SNPs (D′ ≈ 0.40, r2 ≈ 0), indicating independent inheritance. PTPN22 expression was modestly upregulated in TB patients (mean fold change = 1.2 vs. 1.0 in controls), though the difference was not statistically significant (p > 0.05), possibly reflecting compensatory immune regulation in variant carriers. The PTPN22 rs33996649 (R263Q) variant shows a significant independent association with TB susceptibility, highlighting its role as a genetic risk factor and potential target for immunogenetic research.
Lung cancer remains one of the deadliest cancers, both in terms of the incidence and mortality rates. Although a combination therapy comprising immune checkpoint inhibitors and chemotherapy has become the standard therapy for driver gene-negative lung adenocarcinoma, its efficacy is yet to be further improved. Additionally, new treatment methods still need to be developed. Acetylcholinesterase (AChE) has emerged as a potential therapeutic target in various cancers. However, its role in lung adenocarcinoma remains poorly understood. This study aims to investigate the role of AChE in the progression of lung adenocarcinoma and to design and synthesize small-molecule compounds targeting AChE for exploring their potential as novel therapeutic agents. AChE is significantly overexpressed in lung adenocarcinoma. Therefore, we synthesized two novel AChE inhibitors and characterized them by nuclear magnetic resonance and high-resolution mass spectrometry. Subsequently, two inhibitors were added to lung adenocarcinoma A549 and H1975 cells to detect changes in their biological behaviors such as cell proliferation, apoptosis, cell cycle, and colony-formation ability. Simultaneously, a mouse transplant tumor model was constructed and an AChE inhibitor was injected intraperitoneally to observe changes in the volume and weight of the mouse transplant tumor. Our AChE inhibitors showed significant cytotoxicity against A549 and H1975 cells. They can effectively inhibit cell proliferation, induce apoptosis, prevent cell cycle progression, and reduce colony-formation ability. The mouse transplant tumor model confirmed that they can inhibit cell proliferation. The tumor volume and weight were significantly reduced in the intraperitoneal injection inhibitor group. Notably, the inhibitor did not cause pathological damage to normal organs. Our novel AChE inhibitors can potentially be used to treat lung adenocarcinoma and to develop a promising new direction for future lung adenocarcinoma treatments.
Genetic, epigenetic, and transcriptomic analyses have stratified medulloblastoma (MB) into four canonical subgroups of Wingless Type (WNT), Sonic Hedgehog (SHH), and Group 3 and Group 4, with distinct patient profiles and prognoses. Recent classification strategies have also considered combining Group 3 and Group 4 tumors into a Non-WNT/Non-SHH subgroup to account for biological overlap and heterogeneity. Using high-dimensional gene expression data from 487 pediatric and young adult patients and over twenty-one thousand transcripts, this study explores which genes can improve prognostic accuracy for survival while accounting for molecular stratification, histological subtype, key oncogenic drivers (MYC and MYCN amplification), and established clinical covariates, including age group (< 3 vs. 3–21 years) and metastatic status. We then develop a multi-stage framework for identifying prognostic genes and evaluating modern survival modeling strategies. In the first stage, gene screening was performed using Benjamini–Hochberg adjusted Cox regression across false discovery rate (FDR) thresholds from 1
Non-syndromic familial thoracic aortic aneurysm and dissection (ns-FTAAD) is an inherited disease that follows an autosomal dominant pattern; however, pinpointing the responsible genes is often complex. The MYLK gene has been identified as one implicated in TAAD, which necessitates careful and specialized clinical oversight. Systematically gathering evidence on the disease-causing potential of rare genetic variants through detailed family studies is crucial for developing more effective treatment protocols for individuals with this life-threatening hereditary condition. This study reports the identification of a novel pathogenic variant causing ns-FTAAD and provides a comprehensive review of all associated TAAD variants. We report an Iranian family with ns-FTAAD associated with a novel MYLK germline variant. We evaluated all relevant clinical and genetic information. Whole-exome sequencing (WES) was used for variant detection, and Sanger sequencing was performed for validation. A literature search for all TAAD types was conducted on PubMed. The extracted data included the total number of patients studied, the subset with MYLK variants, specific nucleotide and protein changes, patient demographics, pathological features, and clinical symptoms. Exome sequencing led to the identification of a novel variant, NM_053025.4:c.2208_2230dup (p.Ile744Argfs*9), that led to a premature stop codon and nonsense-mediated decay. Five people were variant carriers and three people were non-carriers. A total of 1,440 patients clinically diagnosed with TAAD were recruited in these studies, among whom 59 were carriers of an MYLK variant. Among the 34 variants collected, the distribution was as follows: missense (58.82
Fluoroquinolone-resistant Escherichia coli is a major global clinical threat, particularly in low- and middle-income countries like Nigeria. However, the full genomic landscape, including the relative contributions of chromosomal mutations, plasmid-mediated resistance, and the role of high-risk clones, remains poorly characterized in this setting. This study aimed to define the genomic mechanisms, clonal distribution, and genotype–phenotype relationships of fluoroquinolone resistance in clinical E. coli isolates from Nigeria. A cross-sectional study of 107 clinical E. coli isolates was conducted. Phenotypic susceptibility to ciprofloxacin and nalidixic acid was determined using VITEK 2 and broth microdilution. Whole-genome sequencing was performed, and analysis included detection of quinolone resistance determining region (QRDR) mutations (gyrA, parC, parE) and plasmid-mediated quinolone resistance (PMQR) genes, multilocus sequence typing (MLST), and phylogenetic analysis. Statistical associations were evaluated using chi-squared tests or Fisher’s exact tests. Ciprofloxacin non-susceptibility was high at 86.0
Elective genomic sequencing (EGS) returns monogenic disease findings in multiple genes, including potentially novel variants, and may also provide participants with carrier status, pharmacogenomic and other health-related information. The PeopleSeq Study assessed participants’ motivations for and concerns about EGS and the associated clinical and psychosocial outcomes across diverse EGS providers. We administered a shared questionnaire to participants who chose to undergo EGS via 18 academic, clinical, or commercial EGS platforms. We enrolled 1575 participants, of whom 1147 (72.8
This study aimed to identify and validate robust prognostic biomarkers for oropharyngeal squamous cell carcinoma (OPSCC), with a specific focus on the high-risk HPV-negative subtype. Methods: Integrated bioinformatics analysis was performed on transcriptomic data from four GEO datasets (n = 418 samples). Differentially expressed genes (DEGs) were identified, and a protein-protein interaction (PPI) network was constructed for the most dysregulated genes. Key modules were analyzed via survival analysis and multivariate Cox regression. The top candidate genes were validated at the protein level using immunohistochemistry (IHC) in an independent cohort of 304 OPSCC patients. Results: A 33-gene module related to extracellular matrix organization showed significant prognostic association. It stratified patients into high- and low-risk groups with markedly different overall survival (HR = 2.71, p < 0.001). From this module, SPP1 and PLAU were identified as independent prognostic factors through multi-step screening. Both genes were significantly overexpressed in tumors (approximately 20-fold and 10-fold, respectively, p < 0.001), with high expression strongly correlated with advanced tumor stage (p < 0.01) and, notably, the HPV-negative subtype (p < 0.001). In survival analysis, high expression of either SPP1 or PLAU was associated with poorer overall survival (SPP1: p < 0.001; PLAU: p < 0.001) and progression-free survival (p < 0.001). IHC validation confirmed high protein expression in 69.7
Abstract Background Plasmodium falciparum is the main cause of malaria-related illness and death in sub-Saharan Africa. Despite control efforts, asymptomatic carriers, particularly children, continue to sustain transmission. Improving surveillance requires a better understanding of the genetic diversity and parasite burden of symptomatic versus asymptomatic infections. Objective To compare Plasmodium falciparum genotypic profiles and msp 2 gene copy numbers in symptomatic and asymptomatic children in Kindu, and assess associations with clinical status. Methods Children aged 6 months to 12 years were recruited from health centres and schools. DNA extracted from dried blood spots (Chelex ® 100) was analysed by nested PCR to identify msp 2 allelic families (FC27, 3D7, multiplicity of infection) and by quantitative PCR to estimate copy number. Statistical tests compared groups and predictors of symptomatic infection. Results Of the 522 children included, those in the symptomatic group were younger than those in the asymptomatic group (mean age: 5.77 vs. 7.25 years; p < 0.001) and were more frequently male (70%). P. falciparum prevalence was higher among symptomatic children (69.8%). The FC27 allele family and polyclonal infections (higher multiplicity of infection) were strongly associated with symptomatic malaria (aOR = 6.50 and 24.58, respectively; p < 0.01). Gene copy number was higher in symptomatic and polyclonal infections, but was not independently associated with clinical status after multivariable adjustment (aOR = 0.98; p = 0.134). Parasite positivity remained a strong independent predictor of symptomatic disease (aOR = 3.83; p < 0.001). Conclusion Symptomatic malaria in children is more closely associated with parasite genotype diversity than density. This emphasises the importance of control strategies for molecular surveillance.
Abstract Background Aortic dissection (AD) is a life-threatening cardiovascular disease with limited effective therapeutic options. Phenotypic switching of aortic vascular smooth muscle cells (VSMCs) from a contractile to a pathological state is a critical driver of AD progression. However, the molecular regulators governing this transition remain incompletely understood. This study aimed to identify a critical regulator of VSMC phenotypic switching in AD and to investigate its underlying mechanisms and translational relevance. Methods Single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing datasets obtained from the Gene Expression Omnibus (GEO) database were integrated for analysis. To enhance robustness and reduce dataset-specific bias, weighted gene co-expression network analysis (WGCNA) was performed in both aortic aneurysm (AA) and AD cohorts to identify gene modules associated with VSMC function. Overlapping VSMC-related modules were intersected to define candidate genes. Key regulators were further prioritized in AD datasets using LASSO regression and validated by single-cell RNA sequencing (scRNA-seq) pseudotime trajectory analysis to delineate dynamic gene expression during VSMC phenotypic switching. Functional validation was conducted in an angiotensin II (Ang II)-induced experimental AD mouse model with AAV9-mediated CASQ2 overexpression, as well as in primary VSMCs isolated from the abdominal aorta of mice and treated with Ang II in vitro. Aortic morphology, medial calcification, VSMC phenotypic markers, intracellular Ca 2+ homeostasis, and endoplasmic reticulum (ER) stress signaling were systematically evaluated. Results WGCNA identified a conserved gene module comprising 64 genes associated with VSMC phenotypic transition. Integrative LASSO and scRNA-seq analyses prioritized CASQ2 as a key gene with reduced expression in AD VSMCs. Pseudotime analysis revealed progressive downregulation of CASQ2 during osteochondrogenic phenotypic switching. In AngII-induced experimental AD mice, CASQ2 expression was decreased in the aortic media and accompanied by enhanced medial calcification. In vivo, Ang II infusion markedly reduced aortic CASQ2 expression and induced medial dilation and calcification, accompanied by increased mortality. AAV9-mediated CASQ2 overexpression significantly improved survival, attenuated aneurysmal enlargement, reduced vascular calcification and partially restored contractile marker expression. In vitro, Ang II stimulation decreased CASQ2 levels in primary VSMCs, promoted osteochondrogenic marker expression, and induced intracellular Ca²⁺ overload. CASQ2 overexpression restored calcium-release complex components, suppressed cytosolic Ca²⁺ elevation, and markedly reduced ER stress activation. Conclusions CASQ2 may represent a VSMC-enriched functional regulator involved in AD-associated phenotypic switching through calcium homeostasis and ER stress. These findings suggest that CASQ2 represents a potential therapeutic target in AD. Further studies are needed to determine its disease specificity and translational relevance.
Kyphoscoliotic Ehlers-Danlos syndrome (kEDS, OMIM: #225400) is a rare subtype of Ehlers-Danlos syndrome characterized by joint hypermobility and spinal deformity, with occasional vascular complications. The rarity of vascular phenotypes in kEDS often leads to low clinical suspicion, contributing to delayed diagnosis and poor outcomes. We report a 13-year-old boy who presented with joint laxity, scoliosis, blue sclerae, and pectus excavatum, and who ultimately succumbed to aortic rupture. Initial whole-exome sequencing (WES) and copy number variation (CNV) analysis failed to identify a causative variant, and genes associated with Marfan syndrome were excluded by WES and multiplex ligation-dependent probe amplification (MLPA). Upon re-analysis of the WES data, however, a homozygous deletion spanning exons 15–16 of PLOD1 was detected and subsequently confirmed by quantitative PCR. This case demonstrates that small exon deletions in PLOD1 may not be reliably detected by routine WES/CNV pipelines, leading to diagnostic delay, and underscores the underrecognized vascular risk in kEDS. Clinicians should maintain vigilance for vascular complications in patients with kEDS and consider re-analysis strategies to ensure timely diagnosis and appropriate genetic counseling.
Our study investigated the association between transcription factor 7-like 2 (TCF7L2-rs7903146), angiotensin convertase enzyme (ACE-rs4646994), angiotensinogen (AGT-rs699), angiotensin II type 1 receptor (AGT1R-rs5186), fat mass and obesity-associated (FTO-rs17817499) and melanocortin 4 receptor (MC4R-rs17782313, rs12970134 and rs229616) single nucleotide polymorphisms (SNPs) with type 2 diabetes (T2D), obesity and hypertension in a Black South African population. This cross-sectional study involved 560 Black South Africans aged 25 to 74 years. Participant demographic and lifestyle characteristics were self-reported; anthropometry and blood pressures (BP) measured; oral glucose tolerance tests used to diagnose T2D; and SNPs genotyped by polymerase chain reaction. The Benjamini-Hochberg method was used to control for multiple hypothesis testing, using a significance threshold of 0.12. Using the median test, systolic BP was significantly higher in carriers of the G/G genotype of rs229616 within the MC4R gene compared to carriers of the G/A genotype (p = 0.006, p-FDR = 0.030). In the same gene, logistic regression analysis showed that carriers of the minor C/C genotype of the rs17782313 SNP had a significantly higher risk of hypertension (OR = 1.37, p = 0.023, p-FDR = 0.115) in the unadjusted model. However, the significance was attenuated after adjusting for age, gender and BMI (OR = 1.32, p = 0.084, p-FDR = 0.140). Moreover, carriers of the minor T/T genotype of the TCF7L2 rs7903146 SNP had a lower risk of T2D in the crude model (OR = 0.66, p = 0.043, p-FDR = 0.108) and after adjustment for age, gender and BMI (OR = 0.63, p = 0.041, p-FDR = 0.108). These findings remained significant after correction for multiple comparisons. TCF7L2-rs7903146 (C/C genotype) and MC4R-17,782,313 (C/C genotype) SNPs are potential genetic risk factors for T2D and hypertension, respectively, in the Black South African population. Replicating these findings and exploring the role played by these genetic variants in downstream molecular pathways could aid in risk stratification and facilitate personalized approaches to healthcare delivery.
TANGO2 deficiency disorder (TDD) is a rare autosomal recessive condition characterized by recurrent metabolic crises, rhabdomyolysis, encephalopathy, seizures, intellectual disability, and life-threatening cardiac arrhythmias. Here, we describe 16 affected individuals from 10 consanguineous Palestinian families harboring a shared homozygous missense variant in TANGO2 (NM_152906.7:c.443T > G; NP_690870.3:p.(Leu148Trp)). Exome sequencing identified the variant in three probands and targeted Sanger sequencing confirmed segregation in all remaining families. The variant is absent from population databases and is predicted to be deleterious by multiple in silico tools. Microsatellite marker analysis was performed using five short tandem repeat (STR) markers spanning the TANGO2 locus. Clinical presentation was heterogeneous, including developmental delay, recurrent encephalopathy, rhabdomyolysis, seizures, and cardiac involvement. Microsatellite marker analysis revealed a conserved ancestral haplotype flanking the TANGO2 locus in all genotyped affected individuals, supporting a founder effect in this population. Supportive management including coenzyme Q10 and B-complex vitamins (B-100) was commonly used; consistent with prior reports, some families described reduced frequency and/or severity of spells following supplementation. These findings provide strong clinical, genetic, and haplotype evidence supporting reclassification of the TANGO2 p.(Leu148Trp) variant as likely pathogenic and highlight the importance of early molecular diagnosis and targeted screening strategies in high-consanguinity populations.
PDZK1IP1 is implicated in various cancers, but its role in hepatocellular carcinoma (HCC) remains unclear. To investigate the expression, clinical significance, and biological function of the miR-4512/PDZK1IP1 axis in HCC. Serum samples from 56 HCC patients, 57 cirrhosis patients, and 68 healthy controls were analyzed by qRT-PCR. Diagnostic and prognostic values were assessed by ROC curves and Kaplan-Meier/Cox regression analyses, respectively. The regulatory relationship was validated by dual-luciferase assay. Functional roles and downstream mechanisms were examined via cellular assays and Western blotting. Serum miR-4512 was significantly downregulated while PDZK1IP1 was upregulated in HCC patients, showing a negative correlation. Both markers served as independent prognostic factors for overall survival and disease-free survival. A triple diagnostic combination (miR-4512 + PDZK1IP1 + AFP) achieved an outstanding AUC of 0.988. Dual-luciferase assay confirmed miR-4512 directly targeted the 3’UTR of PDZK1IP1. Functionally, miR-4512 overexpression or PDZK1IP1 silencing suppressed HCC cell proliferation, migration, and invasion. Mechanistically, Western blot revealed that miR-4512 suppressed the Akt/mTOR signaling pathway and glycolysis, which was robustly reversed by PDZK1IP1 overexpression. The miR-4512/PDZK1IP1 axis regulates HCC progression via the Akt/mTOR and glycolysis pathways. Both molecules demonstrate significant potential as robust diagnostic and prognostic biomarkers for HCC.
Angiotensin-converting enzyme 1 (ACE1) gene polymorphisms have been suggested to influence susceptibility to and severity of coronavirus disease 2019 (COVID-19) through dysregulation of the renin–angiotensin system. Despite considerable research on COVID-19, the influence of genetic factors, particularly polymorphisms in the ACE gene, on disease severity in pediatric populations remains inadequately understood. Therefore, the present study aimed to investigate the association of ACE1 insertion/deletion (I/D) polymorphism and ACE1 variants rs4341 and rs4343 with clinical manifestations, laboratory findings, and disease severity in hospitalized children with COVID-19. This study included 100 hospitalized pediatric patients with confirmed COVID-19 infection. Demographic characteristics, including age and sex, clinical manifestations, comorbidities, disease severity, laboratory findings, ICU hospitalization, and mortality outcomes were recorded. Genotyping of the ACE1 I/D polymorphism was performed using PCR-based methods, while rs4341 (C/G) and rs4343 (A/G) polymorphisms were analyzed using PCR-restriction fragment length polymorphism (PCR-RFLP) assays. Among the 100 enrolled patients, 76
