Search Results (10,689)

Background: Chronic kidney disease (CKD) in children is frequently associated with underlying genetic etiologies, particularly in cases with early onset, congenital anomalies, or multisystem involvement. The integration of molecular diagnostics into routine nephrological practice represents an important step toward personalized medicine in pediatric CKD. Methods: This retrospective observational study included 50 pediatric patients with CKD stages 2–5 and suspected hereditary etiology evaluated at a tertiary pediatric center. All patients underwent genetic testing using next-generation sequencing and/or chromosomal microarray analysis. Clinical characteristics, CKD stage, extrarenal manifestations, and disease progression were analyzed in relation to genetic findings. Associations between clinical variables and genetic diagnosis were assessed using appropriate statistical tests, including multivariable logistic regression. Results: A positive genetic diagnosis was identified in 28 patients (56%), including 21 monogenic disorders detected by next-generation sequencing and 7 pathogenic copy number variants identified by chromosomal microarray analysis. Extrarenal manifestations were present in 48% of patients and were significantly associated with a higher diagnostic yield (75% vs. 42.3%; OR = 4.09; 95% CI: 1.23–13.61; p = 0.007). Psychomotor delay was strongly associated with pathogenic copy number variants (p < 0.001). Patients with confirmed genetic etiologies exhibited significantly higher rates of CKD progression compared with genetically negative individuals (82.1% vs. 22.7%; OR = 15.64; 95% CI: 3.90–62.7; p < 0.001). In multivariable analysis, genetic diagnosis shows association with disease progression after adjustment for age and baseline renal function. Conclusions: Genetic testing provided a molecular diagnosis in more than half of children with CKD and suspected hereditary etiology. Extrarenal manifestations were strongly associated with a higher diagnostic yield, while confirmed genetic etiologies may be associated with CKD progression. These findings support the early integration of genetic diagnostics into the evaluation of pediatric CKD to improve prognostic assessment and enable more personalized management strategies. Full article

Kidney development in the first 1000 days of life is vulnerable to numerous prenatal, perinatal, and congenital factors. This review aims to analyze the main determinants of early kidney development and to highlight the role of pediatricians in identifying at-risk infants and implementing preventive strategies to reduce the risk of chronic kidney disease (CKD). For at-risk newborns, early assessment of kidney size and function is essential for the timely detection of functional decline. Key risk factors include prenatal exposures, perinatal complications, genetic conditions, and postnatal factors. Early, tailored nephrological follow-up is crucial for preventing CKD and its complications. Determining optimal monitoring intervals through clinical, laboratory, and ultrasound evaluations enables risk stratification, ensuring closer surveillance for the most vulnerable infants during this critical window. This review integrates evidence from experimental, epidemiological, and clinical studies and highlights the importance of early-life interventions in shaping renal health across the lifespan. Full article

Genetic diversity and antifungal susceptibility profiles of Aspergillus fumigatus are critical for understanding the evolution of resistance in clinical and environmental settings. We performed comprehensive genomic characterization of A. fumigatus isolates using whole-genome sequencing combined with phenotypic susceptibility assays. SnpEff-based variant annotation identified 76,079 single-nucleotide polymorphisms, revealing a high proportion of mutations (78.8%) in upstream and downstream regulatory regions, whereas high-impact coding variants remained rare (0.083%). Several key mutations were identified, including the well-established cyp51A M220V and HMG1 S212P/Y564H mutations. Moreover, a diverse array of peripheral cyp51A polymorphisms (M39I, E402D, N248K, and K372N) was detected, although these variants did not correlate with the resistant phenotypes. Our comparative genomic analysis identified a novel A586T substitution in the FKS1 gene in an isolate with an elevated minimum effective concentration of caspofungin, suggesting its possible association with reduced susceptibility, although functional validation is required. In isolates lacking canonical target-site mutations, the high frequency of regulatory-region variants indicated the involvement of non–target-site mechanisms. This study provides a detailed map of the genomic landscape of A. fumigatus and identifies candidate loci for future functional validation. Our results demonstrate the utility of high-throughput genomic surveillance for monitoring emerging resistance trends and characterizing the genetic background of clinical fungal pathogens. Full article

Linezolid represents a critical last-resort treatment for severe multidrug-resistant (MDR) Gram-positive bacterial infections. Rising linezolid resistance in Enterococcus isolates threatens its efficacy; this study characterized the molecular features and transfer potential of plasmid-encoded linezolid resistance genes optrA and poxtA in a linezolid-resistant Enterococcus asini isolate from chickens. An E. asini strain was isolated during a surveillance program focusing on drug-resistant Gram-positive bacteria in poultry. PCR screened linezolid resistance genes, conjugation and plasmid stability assays evaluated gene transferability and stability, and whole-genome sequencing (WGS) was performed using both the Illumina and Nanopore platforms. We present the first detection of optrA and poxtA genes in E. asini recovered from chicken feces in China. Sequence analysis of the complete genome showed that poxtA and optrA were situated on two distinct plasmids. The poxtA positive plasmid, pHNGXN23C145Ea-1, also carried multiple resistance genes, including tet(S), fexB, erm(B), ant(6)-Ia, aph(3′)-III. Furthermore, the poxtA gene was flanked by IS1216E mobile elements. The optrA bearing plasmid, pHNGXN23C145Ea-2, harbours a common genetic array of ‘IS1216E fexA-optrA-erm(A)-IS1216E’. Conjugation experiments indicated that neither the poxtA- nor the optrA-bearing plasmid was transferred to recipient strains, which was consistent with sequence analysis showing that both plasmids lacked intact conjugative transfer regions. Stability assays confirmed that poxtA and optrA remained highly stable in the absence of selective pressure. Notably, this discovery was made in a livestock sample, despite the non-use of linezolid in food animals, suggesting that such niches may act as silent reservoirs for resistance genes, which could persist and potentially transfer to clinically relevant MDR pathogens. Full article

Background: Familial hemiplegic migraine (FHM) is a rare and severe form of migraine disorder featuring aura symptoms that include hemiplegia during attacks. While pathogenic missense variants in CACNA1A, ATP1A2, and SCN1A can cause FHM or its sporadic form, they explain less than 20% of suspected hemiplegic migraine cases, suggesting the involvement of other genes or genetic variations, potentially including copy number variations (CNVs). PPRT2 gene variants including CNVs have also been implicated in hemiplegic migraine. Methods: Multiplex ligation-dependent probe amplification (MLPA) assays were used to investigate the presence of CNVs in the CACNA1A, SCN1A, ATP1A2, and PRRT2 genes in a cohort of 170 unrelated probands suspected to have FHM who had tested negative for pathogenic missense or small indel variants within these genes. Potential CNVs were subsequently confirmed using quantitative PCR. Results: In 15 patients referred for FHM genetic testing, various CNVs in the target genes were detected by MLPA and subsequently validated by quantitative PCR. CACNA1A exon duplications were identified in six patients and deletions found in two. Two patients had ATP1A2 exon deletions, while one had a duplication. For SCN1A, exon deletions were found in three patients and a duplication in one. PRRT2 exon deletions were detected in five patients, with a single nucleotide polymorphism (SNP) array confirming a deletion spanning PRRT2 and neighbouring loci including 26 genes in one of those. Three patients had CNVs in more than one FHM gene. Conclusions: Our study demonstrates the presence of CNVs in FHM genes in a subset of hemiplegic migraine cases (~9%), suggesting a likely role in the disorder and highlighting the need to explore structural variation in addition to the commonly interrogated genetic mutation points. These findings contribute to further understanding of genetic mechanisms that underlie hemiplegic migraine and may inform improved diagnostic and therapeutic strategies. Full article

Objective: Increased nuchal translucency (NT) thickness at 10–14 weeks’ gestation is a well-established marker of chromosomal abnormalities, foetal structural defects, genetic syndromes, and foetal death; however, its association with foetal central nervous system (CNS) abnormalities has not been systematically evaluated. This study aimed to review and synthesise existing evidence on the relationship between first-trimester increased NT and prenatal ultrasound–detected foetal CNS abnormalities. Methods: A systematic literature search of MEDLINE, Embase, and CINAHL was conducted in accordance with PRISMA guidelines and registered in PROSPERO. Studies reporting increased NT in singleton pregnancies and structural abnormalities of the foetal CNS identified on prenatal ultrasound were included. Study selection, data extraction, and quality assessment were performed independently by two reviewers. Results: Twenty-three studies, including 15,592 euploid pregnancies with increased NT, met the inclusion criteria. Definitions of increased NT varied across studies, most commonly >95th centile or ≥3.5 mm. The pooled prevalence of CNS anomalies was 1.16% (95% CI 0.68–1.95; I² = 80%). In three comparative studies including 6040 pregnancies with increased NT and 152,682 with normal NT, increased NT was associated with higher odds of CNS anomalies (OR 3.22, 95% CI 1.52–6.80; I² = 74.1%). Conclusions: These findings suggest that euploid foetuses with increased NT may have a higher risk of CNS abnormalities. Full article

Background/Objectives: The Black Caribbean population of Honduras, also referred to locally as Negro Inglés, constitutes one of the country’s nine recognized indigenous and Afro-descendant peoples. Predominantly settled in the Bay Islands and sections of the Caribbean coast, this community traces its ancestry predominantly to West Africa and has remained culturally and linguistically distinct for more than three centuries. Despite its demographic and historical relevance, no population-specific short tandem repeat (STR) database has been established for this group. Methods: Allele frequencies for 23 autosomal STR loci were characterized in 100 unrelated Black Caribbean individuals from the department of Islas de la Bahía. DNA was extracted from blood on FTA cards and amplified with the PowerPlex Fusion 6C System (Promega Corporation). Statistical parameters were computed using Genepop v4.2, Arlequin v3.5 and GDA v1.0. Results: A total of 241 distinct alleles were detected across all 23 loci (mean 10.48 ± 3.85 alleles/locus). Expected heterozygosity ranged from 0.6541 (D13S317) to 0.9350 (SE33), with a mean of 0.8150 ± 0.0664—values consistent with a population of predominantly West African origin. No locus exhibited a significant departure from Hardy–Weinberg equilibrium after Bonferroni correction (α = 0.0022). The combined power of discrimination exceeded 99.9999% and the combined chance of exclusion surpassed 99.9999%. Conclusions: This first genetic characterization of the Honduran Black Caribbean population delivers an essential, population-specific reference dataset for forensic casework, paternity testing, and population genetics research. The data also deepen the understanding of Afro-descendant genetic diversity in Central America and constitute a critical step towards equitable forensic genetic services for all Honduran ethnic communities. Full article

Background: Resistance to first-line anti-tuberculosis drugs in Mycobacterium tuberculosis represents a significant public health challenge, particularly in high-burden tuberculosis (TB) settings such as Pakistan, where multidrug-resistant (MDR) forms further complicate disease control efforts. Drug resistance is primarily associated with mutations in rpoB, inhA, katG, embA, embB, embC, and pncA. The emergence of novel, region-specific variants underscores the urgent need for integrating genomic surveillance into routine TB diagnostics and regional control programs. This study aimed to identify the spectrum of mutations contributing to first-line drug resistance in MDR-TB isolates from Khyber Pakhtunkhwa, Pakistan. Methods: Whole-genome sequencing was performed on 16 clinical isolates (12 MDR and 4 drug-susceptible) to identify resistance-associated mutations in rpoB, inhA, katG, embA, embB, embC, and pncA. Detected variants were interpreted using the World Health Organization (WHO) mutation catalogue to determine their association with drug resistance. Phylogenetic relationships were inferred using the Bacterial and Viral Bioinformatics Resource Center (BV-BRC) platform. Results: A total of 16 M. tuberculosis isolates were analyzed to evaluate resistance to first-line anti-tuberculosis drugs. In rpoB, 76 distinct variants were identified, including canonical mutations such as Ser450Leu and His445Arg, as well as a potentially novel substitution, Ser431Phe, predicted to confer high-level rifampicin resistance. The katG and inhA genes harbored 24 and 27 mutations, respectively, including well-characterized substitutions such as Ser315Thr and Ala114Glu, which are strongly associated with isoniazid resistance. Mutations in embA and embB were linked to ethambutol resistance, with several variants localized within conserved transmembrane domains critical for drug interaction. Phylogenetic analysis revealed substantial genetic diversity and evidence of local transmission among MDR-TB isolates. Conclusions: This study suggests that the genetic landscape of drug resistance in M. tuberculosis is highly dynamic in endemic regions. The findings highlight the importance of integrating region-specific mutation profiles into molecular diagnostic frameworks to enhance early detection, guide individualized therapeutic interventions, and strengthen strategies aimed at controlling the transmission of MDR-TB. Full article

Asthma is a chronic respiratory disease characterized by airway hyperresponsiveness, obstruction, and persistent inflammation, arising from complex interactions among genetic, epigenetic, immune, and environmental factors. To elucidate the stage-specific molecular mechanisms underlying asthma progression, we constructed candidate genome-wide genetic and epigenetic networks (GWGENs) of human cells through large-scale biological database mining. Using a system order detection scheme, false-positive interactions were pruned to identify real GWGENs corresponding to three clinical stages of asthma: quiet, exacerbation, and follow-up. Core GWGENs were subsequently extracted from each real network using the principal network projection (PNP) method to highlight dominant regulatory structures and pathogenic pathways. Based on the inferred core networks, key stage-specific biomarkers were identified and further explored as potential drug targets. Drug–target relationships were investigated by integrating gene expression perturbation profiles from the Connectivity Map (cMap), comprising microarray data for 14,207 genes across 1327 compounds. This network-guided analysis enabled the qualitative design of multi-molecule drug combinations tailored to each disease stage. Our results suggest that asthma onset is associated with reduced innate immunity, increased disease susceptibility, and impaired endothelial barrier recovery influenced by microenvironmental factors such as cigarette smoke and lipopolysaccharides, together with genetic and epigenetic alterations. During the exacerbation stage, enhanced differentiation of T cells toward the T helper 2 lineage contributes to airway inflammation and tissue injury. In the follow-up stage, T helper 1–mediated responses are linked to mucus hypersecretion, airway obstruction, and sustained inflammation. Collectively, these findings demonstrate that a systems-level, network-based framework can uncover stage-specific pathogenic mechanisms of asthma and provide hypothesis-generating insights for network-informed drug repurposing strategies. Full article

X-linked dystrophin-deficient muscular dystrophy (DD-MD) is an uncommon neuromuscular disorder in cats. We described an adult male cat with chronic tongue protrusion, dysphagia, muscle hypertrophy, and a history of rhabdomyolysis associated with anesthesia. Clinical pathology revealed markedly increased CK activity, muscle histopathology demonstrated a dystrophic phenotype, and an absence of dystrophin protein was confirmed by immunofluorescent staining. Whole genome sequencing identified two potential disease-causing variants, including a new missense variant in the DMD gene (c.2207T>C; p.Gln736Arg), which was considered causative of the clinical phenotype. A second variant in the CLIC2 gene was also detected but was considered unlikely to cause myopathic signs. The clinical course remained stable over 1.5 years with supportive management and dietary modification, and no further episodes of rhabdomyolysis occurred. This case expands the known spectrum of feline DMD variants and highlights the value of genetic testing combined with muscle histopathology for diagnosing chronic presentations of MD. Avoidance of inhalant anesthetics may be important in managing affected cats due to the risk of acute muscle injury. Full article

Background/Objectives: The widespread adoption of short tandem repeat (STR) marker technology in genetic analysis has led to the collection of substantial STR data from diverse populations. Allele-frequency data provide robust forensic utility and support accurate likelihood ratio calculations, highlighting the importance of regional databases. Methods: The presented study aimed to determine the allelic frequencies and statistical parameters for 16 autosomal genetic STR markers included in the NGM Detect^TM PCR Amplification Kit in a population sample of 220 unrelated individuals from the South-West region of the Republic of Bulgaria. Results: We found that the most polymorphic and informative marker for the Bulgarian population in the southwestern region is SE33, with the next most informative markers being D1S1656, D12S391, D18S51, and FGA. In contrast, D22S1045, D16S539, and D2S441 showed comparatively lower genetic variability and informativeness. At the same time, no deviations from the Hardy–Weinberg equilibrium were observed for the 16 loci studied. Conclusions: This work not only enriches knowledge of the genetic diversity of the Bulgarian population but also provides the Bulgarian and international justice systems with an objective, scientifically sound basis for expert decision-making. Full article

Cymbidium eburneum Lindl. is a valuable ornamental orchid and breeding parent, but its genetic background remains unclear due to habitat destruction and germplasm mixing. This study developed specific SSR markers to evaluate the genetic diversity and structure of 96 C. eburneum Lindl. accessions from China and Vietnam. Transcriptome analysis identified 47,248 SSR loci. Sixteen polymorphic core primer pairs detected 150 alleles (mean Na = 9.375) with an average Polymorphism Information Content (PIC) of 0.444. Observed heterozygosity (Ho = 0.290) was noticeably lower than expected (He = 0.478), indicating heterozygote deficiency. UPGMA clustering identified eight groups strongly correlated with geography. Principal Coordinate Analysis (PCoA) revealed a clear geographical differentiation pattern, featuring the most genetically cohesive group from Guangxi and more differentiated geographically marginal populations from Hainan and Vietnam. STRUCTURE analysis (K = 2) indicated two main gene pools with signals of genetic admixture. Geographical isolation was suggested as a potential driver of genetic differentiation. The Guangxi population represents a genetically consistent major reservoir, while marginal populations harbor unique variations. These findings provide a scientific basis for germplasm identification, conservation, and parental selection in C. eburneum Lindl. breeding. Full article

Domestication has profoundly shaped the phenotypic differentiation and genetic architecture of Perilla. However, analyses of the morphological difference between its cultivated and weedy forms across its varieties remains incomplete. This study analyzed morphological variation, genetic diversity, population structure, and marker–trait associations of 45 accessions representing the cultivated and weedy forms of two Perilla varieties (P. frutescens var. frutescens and var. crispa) collected from South Korea and Japan. Analyses of ten qualitative and quantitative agronomic traits revealed clear domestication-related differentiation. Cultivated var. frutescens showed larger and heavier seeds, whereas cultivated var. crispa and the weedy accessions were characterized by longer inflorescences and higher floret numbers but smaller seeds. Strong positive correlations were observed among seed-related traits, particularly between seed size and seed weight (r = 0.932), indicating coordinated selection of seed traits. Genetic diversity analysis using 70 SSR markers identified 330 alleles consistent with domestication bottlenecks in cultivated forms while higher diversity was generally retained in the weedy accessions. Population structure, UPGMA clustering, and principal coordinate analyses broadly differentiated the cultivated and weedy accessions, although partial admixture indicated shared ancestry and historical gene flow. Association mapping using Q-based GLM and Q + K MLM models identified 23 significant marker–trait associations involving 16 SSR markers consistently detected across both models. Several markers were associated with multiple traits, implying pleiotropy or tight genetic linkage. Notably, five SSR markers (KNUPF192, KNUPF202, KNUPF207, KNUPF230, and KNUPF238) may represent potential candidate loci for marker-assisted selection to improve seed-related traits in var. frutescens and leaf-related traits in var. crispa. Full article

Deoxynivalenol (DON), a Group III carcinogenic mycotoxin frequently detected in cereals and animal-derived food products, poses serious health risks to animals and humans. In this study, we developed a genetically engineered Saccharomyces cerevisiae strain as a proof-of-concept platform for DON detoxification. The yeast was engineered to co-express two detoxification genes, YTDepA and YTDepB (homologs of DepA and DepB from Devosia mutans 17-2-E-8) originally identified in Youhaiella tibetensis. Concurrently, the pyrroloquinoline quinone (PQQ) biosynthesis gene cluster from Klebsiella pneumoniae was integrated to supply the essential cofactor. Gene expression was verified by qRT-PCR and Western blot. The recombinant strain demonstrated a significant 13.98% detoxification of DON after 72 h of fermentation (p < 0.05), as confirmed by HPLC–MS, while the strain expressing only the PQQ cluster showed no detoxification activity. This study establishes an integrated yeast cell factory for DON detoxification and highlights key limitations to guide future optimization efforts. Full article

Diabetes mellitus is a health issue that is rapidly increasing worldwide, and it affects more than 347 million people globally. It is important to note that the disease can be successfully detected in its early stages, enabling physicians to avoid complications and improve patient outcomes. Despite the fact that machine learning (ML) has been extensively used in diabetes classification, the available solutions tend to place little or no emphasis on feature selection and ensembles, which limits prediction accuracy and generalizability. In this study, we introduce a hybrid framework that is based on three feature-selection algorithms, specifically, genetic algorithm (GA), correlation-based feature selection (CFS) and recursive feature elimination (RFE), in single and hybrid forms, and three classifiers, namely, multi-layer perceptron (MLP), support vector machine (SVM) and random forest (RF), to achieve a greater predictive robustness with the aid of soft voting. Experimental findings obtained from a benchmark diabetes dataset indicate that the RFE + CFS + SVM combination achieves the best performance, with an accuracy of 98.0%, sensitivity of 97.43%, specificity of 99.03%, precision of 99.51% and F1-score of 98.72%. These results indicate that the suggested hybrid feature-selection and ensemble learning model can offer a robust and highly effective approach for early-stage diabetes diagnosis, one which clinicians may use to make timely and accurate decisions. Full article