Disease Phenotype Research Articles

Atopic dermatitis (AD) is the most common inflammatory skin disease in the pediatric population. In recent years, the role of microRNAs in inflammatory and immunological mechanisms as specific biomarkers of AD has received growing attention. The aim of the present study was a quantitative assessment of serum expression levels of miR-100, miR-224 and miR-155 in children with AD compared with healthy peers, and an analysis of their potential associations with clinical disease phenotype, severity of skin lesions (SCORAD), cytokine profile, immunological parameters and the presence of concomitant allergic diseases. The study included 12 children with AD and 9 healthy children. Selected miRNAs were isolated from serum, followed by reverse transcription using universal primers and quantification by qRT-PCR. Children with AD exhibited significantly higher expression levels of miR-155 compared with controls (p = 0.003). No statistically significant differences were observed for miR-100 and miR-224. miR-100 expression was significantly higher in children with a positive history of inhalant allergy compared with those without such a diagnosis (p = 0.014). A positive correlation was observed between miR-100 levels and the percentage of eosinophils (r = 0.599; p = 0.052) as well as absolute eosinophil count (r = 0.600; p = 0.051). MiR-155 is significantly upregulated in children with AD suggesting it as a candidate biomarker worthy of further investigation in larger cohorts. Although miR-100 did not differentiate the groups, its correlation with eosinophilia and inhalant allergy suggests a role in disease phenotyping.

IgA nephropathy (IgAN), first described in 1968, is the most common primary glomerulonephritis worldwide. The prevalence of the disease is highest in Asia compared with Europe and North America, with the possible underdiagnosis in regions such as Africa.Typically, debuting in young patients, IgAN is one of the major causes of the development of end-stage chronic kidney disease, which requires the use of renal replacement therapy. However, recent studies have shown a rising incidence among older individuals, often with more severe outcomes.The time course and prognosis of IgAN remain difficult to predict due to the pronounced polymorphism of clinical manifestations and morphological features, apparently reflecting a wide range of possible etiopathogenesis mechanisms. This literature review discusses current approaches to evaluating clinical symptoms and biomarkers in relation to pathomorphological features and disease prognosis. Traditionally, severe proteinuria has been regarded as the only reliable predictor of poor outcomes and the main indication for active treatment. However, recently evidence highlights the prognostic significance of proteinuria of any level, including persistent microhematuria, suggesting the need to reconsider current therapeutic paradigm. Two long-standing debates over the prognostic role of macrohematuria also remain unresolves. In addition, the review addresses the prognostic value of nephrotic syndrome depending on specific histological patterns, such as IgAN with minimal change disease or endocapillary proliferation. Based on published data, clinical variants of IgAN and their associations with disease outcomes are analyzed. The first results of cluster analysis, which have identified distinct disease phenotypes with differing risks of progression and treatment response, are also presented.

Isotype-selective roles of hepatic acetyl-CoA carboxylases in a mouse model of fatty liver disease

Abstract Background Congenital Central Hypoventilation Syndrome (CCHS) is a rare genetic condition characterised primarily by alveolar hypoventilation which is worse during sleep. Most often caused by mutations in the PHOX2B gene, disease phenotype is varied and can involve multi-system comorbidities such as Hirschsprung’s Disease and neural crest tumours. Children with CCHS often face a high burden of care related to their primary ventilatory insufficiency and comorbidities. Methods We performed a retrospective review of the medical records of all patients with CCHS under the care of our tertiary paediatric centre. Demographic information and relevant clinical data informed by the European CCHS Consortium consensus guidelines were collected. This included age and method of diagnosis, primary presenting symptoms, comorbidities at diagnosis, genotype, methods of screening for complications, incidence of comorbidities, frequency of polysomnography (PSG), ventilation modes, and multi-disciplinary team involvement. Descriptive statistics will identify key clinical characteristics in our population of children with CCHS and highlight management priorities. Data on local management practices will be compared to international standards as published in the recent European CCHS Consortium Project Guidelines. Progress to Date Medical record review has been undertaken, and all demographic and clinical data has been collected for our cohort of children with CCHS (n = 7). Statistical analysis is in progress. Intended outcome and impact This project will paint a picture of the current landscape of CCHS in our tertiary paediatric centre. It will highlight areas of need for children with this complex, chronic condition and guide improvements in the quality of care provided.

The lung is increasingly recognized as an organ with dual endocrine and respiratory roles, participating in a complex bidirectional crosstalk with systemic hormones and local/paracrine activity. Endocrine and paracrine pathways regulate lung development, ventilation, immunity, and repair, while pulmonary cells express hormone receptors and secrete mediators with both local and systemic effects, defining the concept of the "endocrine lung". This narrative review summarizes current evidence on the endocrine-pulmonary axis. Thyroid hormones, glucocorticoids, sex steroids, and metabolic hormones (e.g., insulin, leptin, adiponectin) critically influence alveologenesis, surfactant production, ventilatory drive, airway mechanics, and immune responses. Conversely, the lung produces mediators such as serotonin, calcitonin gene-related peptide, endothelin-1, leptin, and keratinocyte growth factor, which regulate vascular tone, alveolar homeostasis, and immune modulation. We also describe the respiratory manifestations of major endocrine diseases, including obstructive sleep apnea and lung volume alterations in acromegaly, immunosuppression and myopathy in Cushing's syndrome, hypoventilation in hypothyroidism, restrictive "diabetic lung", and obesity-related phenotypes. In parallel, chronic pulmonary diseases such as chronic obstructive pulmonary disease, interstitial lung disease, and sleep apnea profoundly affect endocrine axes, promoting insulin resistance, hypogonadism, GH/IGF-1 suppression, and bone metabolism alterations. Pulmonary neuroendocrine tumors further highlight the interface, frequently presenting with paraneoplastic endocrine syndromes. Finally, therapeutic interactions are discussed, including the risks of hypothalamic-pituitary-adrenal axis suppression with inhaled corticosteroids, immunotherapy-induced endocrinopathies, and inhaled insulin. Future perspectives emphasize mapping pulmonary hormone networks, endocrine phenotyping of chronic respiratory diseases, and developing hormone-based interventions.

Neonatal ichthyosis-sclerosing cholangitis syndrome (NISCH) is an autosomal recessive disorder characterized by cholestasis, generalized ichthyosis, alopecia, and dental anomalies. As this is a rare syndrome, here we present a case caused by a novel mutation followed by a literature review of all published cases. This retrospective review includes all original articles on the clinical profiles of all 37 cases published through December 2024 using a PubMed search. The patient was a 2-month-old boy who presented with cholestasis, sparse hair, and generalized ichthyosis. Whole-exome sequencing revealed a novel pathogenic variation in exon 1 of the CLDN1 gene: (NM_021101.5) c.36dupT (p.Leu13SerfsTer56). The patient was symptomatically managed, and his condition improved. Among the 37 reported cases, the median age at diagnosis was 60 months (range, 1-636 months). Patients of Moroccan ethnicity were most commonly affected, and c.200_201delTT was the most common mutation. Among the clinical features, ichthyosis was universal (37 of 37 [100%]), followed by jaundice in 70.2% (26 of 37), pruritus in 38.2% (13 of 34), hepatomegaly in 43.3% (13 of 30), and splenomegaly in 23.8% (5 of 21) of patients. Portal hypertension (7 of 35 [20%]) and mental retardation (3 of 21 [14.2%]) were rare. The disease phenotype varied from no liver involvement or transient neonatal cholestasis to end-stage liver disease. Progressive liver disease was reported in 8 patients, five of whom underwent liver transplantation. NISCH is a rare syndrome with variable phenotypes ranging from no liver involvement and transient neonatal cholestasis to advanced liver disease requiring liver transplantation. Therefore, a multidisciplinary approach with close follow-up is required.

Bi-allelic deleterious variants in SNAPIN, which encodes a retrograde dynein adaptor, cause a prenatal-onset neurodevelopmental disorder.

Chronic obstructive pulmonary disease (COPD) is a multifactorial disease of the respiratory system and is the third leading cause of death worldwide. In the framework of the most relevant concepts of COPD pathogenesis, the key focus is on accelerated cellular senescence. FOXO family transcription factors are important hub components of cellular senescence signaling pathways. The objective of the study is to identify the association of FOXO1 (rs12585277, rs9549240), and FOXO3A (rs2253310, rs3800231) genes polymorphic variants with COPD and disease phenotypes. DNA samples from COPD patients (N = 710) and healthy individuals (N = 655) were used, polymorphic loci were analyzed by real-time PCR. For the first time, significant associations of FOXO1 (rs12585277) and FOXO3A (rs2253310) gene polymorphic loci with COPD and disease phenotypes were shown. Association with COPD was established with FOXO1 (rs12585277) (Padj = 0.0018, OR = 1.44 for the AG genotype) and FOXO3A (rs2253310) (Padj = 5.926 × 10–7, OR = 1.99 for the GG genotype). A significant genotype-dependent variation of smoking index (in pack/years), vital capacity and forced vital capacity was revealed for FOXO1 (rs9549240, rs12585277) and FOXO3A (rs2253310) loci. Multiple regression and ROC analysis identified highly informative COPD risk model, which included polymorphic variants of the FOXO1 (rs12585277) and FOXO3A (rs2253310) genes, smoking index and age (P = 5.25 × 10–93, AUC = 0.864). The multivariate regression model of the COPD “frequent exacerbator” phenotype included the AG genotype of FOXO1 (rs12585277), smoking index and age (AUC = 0.897, P = 4.1 × 10–86). FOXO family transcription factors involved in autophagy, oxidative stress and cellular homeostasis may provide a platform for a new diagnostic and treatment strategy for COPD as potential biomarkers and targets for therapy.

Multiple system atrophy (MSA) is a sporadic, progressive neurodegenerative disease that affects multiple systems, including the Parkinsonian and cerebellar systems. It is commonly associated with obstructive and central sleep apnea, sleep-related hypoventilation, and stridor, which may evolve with changes in the disease phenotype and severity. These respiratory complications are considered potential causes of sudden death, making the critical importance of their evaluation and management in patients with MSA. However, no established treatment has been developed, and therapeutic approaches, such as continuous positive airway pressure (CPAP) or tracheostomy, have been attempted on a case-by-case basis.

Lvvibriocin-GK effectively reduced skin ulcer syndrome of Apostichopus japonicus by eliminating surface bacteria, modulating gut microbiota, and enhancing host immune responses.

Aging is a major risk factor in amyotrophic lateral sclerosis (ALS) and other adult-onset neurodegenerative disorders. Whereas young neurons are capable of buffering disease-causing stresses, mature neurons lose this ability and degenerate over time. We hypothesized that the resilience of young motor neurons could be restored by reexpression of the embryonic motor neuron selector transcription factors ISL1 and LHX3. We found that viral reexpression of ISL1 and LHX3 selectively in postnatal motor neurons reactivates aspects of their youthful gene expression program and alleviates key disease-relevant phenotypes in the SOD1G93A mouse model of ALS. Our results suggest that redeployment of lineage-specific neuronal selector transcription factors can be an effective strategy to attenuate age-dependent phenotypes in neurodegenerative disease.

Exploring spatiotemporal and kinematic gait parameters in individuals with Parkinson's disease across different motor phenotypes: A comparative study with and without dopaminergic therapy.

Pathogen genotypes and host phenotypes of Mycobacterium abscessus pulmonary disease in Taiwan.

Functional analysis of skeletal muscle in vitro requires maturation and stimuli to induce excitation-contraction coupling as well as a quantitative method to analyze contraction. Electric field stimulation (EFS) has been traditionally used as a method to excite skeletal muscle in vitro and in vivo. A combination of human-induced pluripotent stem cell (hiPS) technology and EFS will lead to recapitulation of functional phenotypes of skeletal muscle diseases. Here, we describe the combinational technology using hiPS technology and EFS to induce the maturation of skeletal muscle and analyze contractile performance in vitro.

Cardiovascular-kidney-metabolic (CKM) syndrome describes the complex, bidirectional interplay among cardiovascular, renal, and metabolic dysfunctions, where impairment in one system accelerates decline in the others. This interconnected pathophysiology significantly elevates the risk and progression of heart disease, particularly heart failure, through mechanisms involving insulin resistance, systemic inflammation, neurohormonal activation, and endothelial dysfunction. In this context, therapeutic strategies targeting heart disease must address the multifaceted drivers of CKM. Recent advances highlight the need for an integrated, patient-centered approach that combines lifestyle interventions with pharmacological treatments tailored to individual cardiovascular risk. While foundational therapies such as RAAS inhibitors and statins remain essential, novel agents now offer additional prognostic and quality-of-life benefits. SGLT2 inhibitors have emerged as a cornerstone therapy, improving outcomes in heart failure with both preserved and reduced ejection fraction, independent of glycemic control. GLP-1 receptor agonists and dual GLP-1/GIP agonists like tirzepatide demonstrate cardiometabolic and renal protection, while finerenone shows promise in diabetic kidney disease and several heart failure phenotypes. These therapies not only target glycemic control but also reduce cardiovascular mortality, hospitalizations, and renal decline. Optimizing cardiovascular outcomes in CKM syndrome requires early, multifactorial therapeutic intervention, informed by evolving evidence and a deeper understanding of the heart–kidney–metabolism axis.

Identification of phenotypes in heart failure with preserved ejection fraction among 8161 patients from 3 Spanish cohorts.

Bacterial wilt, caused by Ralstonia solanacearum, is a major constraint to tomato production globally. To uncover resistance loci and develop efficient molecular tools for breeding, we conducted disease phenotyping over two growing seasons, which revealed consistent variation in resistance and moderate broad-sense heritability (H2 = 0.22–0.28), suggesting a genetic basis. A genome-wide association study (GWAS) was performed on a diverse panel of 267 tomato accessions, evaluated against two R. solanacearum strains. A major resistance locus was identified on chromosome 12, with the strongest association observed at SNP S12_2992992, located within a gene encoding a leucine-rich repeat (LRR) receptor-like protein. Haplotype analysis indicated that the resistance-associated allele is relatively rare (~13.5%) in the population, underscoring its potential value in breeding programs. Functional validation in an F2 population derived from a cross between the susceptible ‘Seedathip6’ and the resistant ‘Hawaii 7996’ confirmed that the TT genotype at S12_2992992 was significantly associated with enhanced resistance. A Kompetitive Allele Specific PCR (KASP) marker was developed for this SNP, facilitating cost-effective and high-throughput selection. Collectively, these findings establish S12_2992992 as a robust and functionally informative marker, offering a valuable tool for accelerating bacterial wilt resistance breeding in tomato through marker-assisted selection.

ABSTRACTBackgroundWe identified a novel ABCD1 variant (c.773T>G, p.Leu258Arg, NM_000033.4) in a Chinese pedigree affected by X‐linked adrenoleukodystrophy (X‐ALD). This missense variant in exon 1 is predicted to be pathogenic and likely constitutes the genetic basis of the disease phenotype in this family.MethodsABCD1 gene sequencing was performed in the Chinese pedigree. The pathogenicity of identified variants was assessed using computational prediction tools. Subcellular localization studies were conducted, and very‐long‐chain fatty acid (VLCFA) levels were quantified in patient‐derived samples.ResultsSequencing analysis identified a hemizygous missense variant in the ABCD1 gene (c.773T>G; p.Leu258Arg). In silico pathogenicity prediction using SIFT and PolyPhen‐2 algorithms classified the p.Leu258Arg substitution as deleterious. Functional characterization revealed that the p.Leu258Arg variant impairs the peroxisomal membrane localization of the ABCD1 protein. Consistent with the established role of ABCD1 in peroxisomal β‐oxidation, individuals harboring this variant exhibited significantly elevated serum levels of VLCFA. Specifically, the C26:0/C22:0 ratio was elevated 2.8‐fold compared to control values, confirming impaired VLCFA metabolism.ConclusionIn accordance with the “Standards and Guidelines for the Interpretation of Sequence Variants” established by the American College of Medical Genetics and Genomics (ACMG), we assessed the pathogenicity of the novel ABCD1 gene variant c.773T>G. This variant meets the following ACMG evidence criteria: PM1 (located within a critical functional domain or mutational hotspot known to lack benign variation); PM2 (absent or observed at very low frequency in population databases e.g., gnomAD, EXAC, 1000 Genomes); PP3 (multiple in silico prediction tools consistently suggest a deleterious effect on the gene or gene product). Integrating this evidence (PM1 + PM2 + PP3), the variant is classified as likely pathogenic based on ACMG guidelines. Experimental data from this study further substantiate the pathogenicity of the c.773T>G variant located in exon 1 of the ABCD1 gene. This finding broadens the spectrum of known pathogenic mutations in ABCD1 associated with X‐ALD and provides crucial information for the molecular diagnosis of affected patients.

Potential targeting of urokinase-type plasminogen activator receptor-formyl peptide receptor signaling to prevent recurrence in posttransplant primary podocytopathies.

A molecular basis of Ferredoxin Reductase (FdxR) mutations that result in mitochondriopathies.