Human Gene最新文献

{"title":"Altered expression patterns of lncRNA MEG3 and LINC01611 in patients with colorectal cancer","authors":"Niloofar Faraji ,&nbsp;Mohammad Almasi ,&nbsp;Majid Mirmazloumi ,&nbsp;Nasim Padasht ,&nbsp;Sahand Sadat Mansouri ,&nbsp;Fatemeh Ghaderibarmi ,&nbsp;Haniyeh Royatpour ,&nbsp;Fatemeh Modaresi ,&nbsp;Kourosh Kazempour Samak ,&nbsp;Fahimeh Abedini Bajgiran ,&nbsp;Tahereh Zeinali ,&nbsp;Narges Eslami ,&nbsp;Dariush Shanehbandi ,&nbsp;Ali Salehzadeh","doi":"10.1016/j.humgen.2025.201470","DOIUrl":"10.1016/j.humgen.2025.201470","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is a major global health challenge, with long non-coding RNAs (lncRNAs) gaining attention as potential diagnostic biomarkers. This study aimed to experimentally validate bioinformatics findings on the expression patterns of maternally expressed gene 3 (MEG3) and LINC01611 in CRC patients from a specific ethnic population while considering associated risk factors. This in vitro study initially recruited 50 patients from a single ethnic group, with 48 completing the analysis after the exclusion of two samples. Two lncRNAs, MEG3 and LINC01611, were selected using Gene Expression Omnibus (GEO) microarray data and identified via R/BioConductor. Paired tissue samples (tumor and adjacent margins) were collected during surgery, and RNAs were extracted. Demographic and clinical data of patients were recorded, and gene expression was analyzed using quantitative real-time PCR (qPCR), with GAPDH as the internal control. Data analysis was performed using GraphPad Prism and SPSS software, with the significance level set at <em>P</em> &lt; 0.05. The mean age of the patients was 59.5 ± 3.53 years, with 58.3 % (<em>n</em> = 28) being male, and 37.5 % of the patients had a history of smoking. The majority of patients had poorly differentiated (41.7 %) and stage II tumor (43.8 %), with lymph node metastasis commonly observed (60.4 %). The Wilcoxon signed-rank test revealed significant downregulation of MEG3 (32.396 fold change)and LINC01611(38.923 fold change) in tumor tissues compared to adjacent margins. A family history of CRC was associated with higher expression levels of MEG3 (1.48-fold, <em>P</em> = 0.038) and LINC01611 (1.03-fold, <em>P</em> = 0.007) in both tumor and margin tissues. Multivariable regression analysis demonstrated that lncRNAs had a significant association with tumor differentiation (<em>P</em> &lt; 0.05), while other variables showed no statistically significant association (<em>P</em> &gt; 0.05). Also, positive correlations were observed between MEG3 and LINC01611 expression levels in tumor (<em>r</em> = 0.649, <em>P</em> &lt; 0.001) and margin (<em>r</em> = 0.424, <em>P</em> = 0.003) tissues. The significant downregulation of MEG3 and LINC01611 in tumor tissues compared to adjacent margin tissues highlights their potential role as tumor suppressors in CRC. These findings support further investigation into these lncRNAs as diagnostic biomarkers.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201470"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144931728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estimating drivers of breast tissue transitions from normal to tumor state","authors":"Swapnil Kumar,&nbsp;Vaibhav Vindal","doi":"10.1016/j.humgen.2025.201506","DOIUrl":"10.1016/j.humgen.2025.201506","url":null,"abstract":"<div><div>Tumor tissues are characterized by dysregulated gene expression patterns leading to altered cellular pathways and molecular functions as a result of their transition from normal to tumor state. Further, tumor-adjacent normal tissues (TANTs), utilized as a control in cancer research, are not molecularly normal and differ from healthy normal tissues. These TANTs represent a distinctive transitional state between normal and tumor states. However, the mechanism underlying this state transition, expression dysregulation, and perturbed regulation remain largely unexplored and elusive. Herein, the transitions of breast tissues from normal and TANT to tumor states were modeled using gene expression and regulation data to estimate key drivers underlying these transitions. As a result, we identified 645 shared driver genes underlying the transitions of breast tissues from the healthy normal state to the adjacent normal and tumor states. Besides, we identified 635 shared driver genes underlying the transitions of TANTs to different subtypes. When we intersected both lists of shared driver genes, 615 commonly shared driver genes across the state transitions were observed. Subsequently, functional annotations of these driver genes revealed their involvement in cell growth and maintenance-related activity. Additionally, key pathways associated with cancer pathogenesis, such as Wnt signaling, Notch signaling, NF-kappa B signaling, and PD-L1 expression and PD-1 checkpoint pathway in cancer, were found significantly enriched with these shared driver genes. Thus, the shared driver genes identified across tissue transitions provide ways forward to devise more efficient diagnostic and therapeutic strategies for early and effective disease management.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201506"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145465897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcription Factor driven gene regulation in Autism Spectrum Disorder","authors":"Nimisha Ghosh ,&nbsp;Walter Arancio ,&nbsp;Tariq Al Jabry ,&nbsp;Raya Al Maskari ,&nbsp;Daniele Santoni","doi":"10.1016/j.humgen.2025.201489","DOIUrl":"10.1016/j.humgen.2025.201489","url":null,"abstract":"<div><div>Autism Spectrum Disorders (ASD) encompass a group of neurodevelopmental disorders in which an affected individual faces challenges in social interaction and communication, along with restricted and repetitive stereotypic behavioral patterns and interests. In this work, we have studied the differential gene regulation between patients and controls, mediated by Transcription Factors (TFs), of key genes involved in ASD. Nine and seven TFs have been identified as potential regulators of the set of syndromic and non-syndromic key high confident genes retrieved by the Simons Foundation Autism Research Initiative (SFARI) database. We have also identified significant couples of Transcription Factor - Target Gene potentially associated with an altered regulation in ASD patients. Consistently, many identified couples are involved in processes associated with brain morphogenesis and development. In this regard, this biased regulation could be the target of some experimental design in order to (1) test this hypothesis and (2) try to target this altered regulation pattern in ASD samples. In conclusion, we would like to emphasize that the present work proposes an effective and reliable computational approach that could be applied to any disease with known key genes and available gene expression data.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201489"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring genetic associations in Parkinson's disease: The role of IL-10; −1087G>a and mir146a; rs2910164 C>G polymorphisms","authors":"Javid Ashtari Mahini ,&nbsp;Zahra Shahbazi ,&nbsp;Maryam Rahimi ,&nbsp;Maryam Seyedolmohadesin","doi":"10.1016/j.humgen.2025.201493","DOIUrl":"10.1016/j.humgen.2025.201493","url":null,"abstract":"<div><h3>Introduction</h3><div>Defining the etiology of multifactorial diseases, such as Parkinson's disease (PD), poses significant challenges in diagnosis, management, and treatment strategies. PD is characterized by progressive neurological degeneration. Current scientific evidence indicates that this condition arises from an intricate interplay of genetic and environmental factors. Notably, single nucleotide polymorphisms (SNPs) identified in various genes have been implicated in enhancing susceptibility to this disease. This study aims to investigate the association of two specific polymorphisms, <em>IL-10</em> gene; −1087 G &gt; A and <em>mir146a</em> gene<em>;</em> rs2910164 C &gt; G, with the prevalence of PD.</div></div><div><h3>Methods</h3><div>This investigation employed a case-control design that included 96 participants in both the case and control groups. The identification of alleles was executed using the Tetra-primer Amplification Refractory Mutation System-Polymerase Chain Reaction (T-ARMS-PCR) method. Subsequent genetic and statistical analyses of the findings were performed utilizing POPGENE and SPSS software.</div></div><div><h3>Result</h3><div>The results indicated that the distribution of <em>mir146a</em> gene SNPs within the control and patient populations did not adhere to Hardy-Weinberg equilibrium. Specifically, the frequency of the G allele in patients diagnosed with PD was significantly lower than that observed in the control cohort. Furthermore, individuals carrying the GC genotype exhibited an elevated risk of developing PD, with <em>p</em>-values &lt;0.05. Conversely, the distribution of <em>IL-10</em> gene SNPs conformed to Hardy-Weinberg equilibrium within both groups, and no statistically significant association was found between <em>IL-10</em> gene SNPs and the risk of PD.</div></div><div><h3>Conclusion</h3><div>The findings from this study suggest that the <em>IL-10</em> gene −1087 G &gt; A polymorphism does not contribute to increased susceptibility to PD within the studied population. Conversely, the <em>mir146a</em> gene rs2910164 C &gt; G polymorphism appears to be associated with PD risk. Notably, the G allele of this SNP correlates with a decreased risk of the disease, while the GC genotype is linked to an increased likelihood of developing Parkinson's disease.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201493"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145465900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural and functional analysis of SOX9 mutations in disorders of sex development (DSD): Integration of clinical data and in silico modeling","authors":"Fatou Diop Gueye ,&nbsp;Mama Sy Diallo ,&nbsp;Arame Ndiaye ,&nbsp;Mame Venus Gueye ,&nbsp;Ndiaga Diop ,&nbsp;Adji Dieynaba Diallo ,&nbsp;Rokhaya Ndiaye ,&nbsp;Oumar Faye","doi":"10.1016/j.humgen.2025.201461","DOIUrl":"10.1016/j.humgen.2025.201461","url":null,"abstract":"<div><div>The <em>SOX9</em> gene, located on chromosome 17q24, belongs to the <em>SOX</em> family of transcription factors and shares over 70 % homology with <em>SRY</em>. It plays a central role in testis differentiation and cartilage formation, notably by regulating key genes such as <em>AMH</em>. Mutations in <em>SOX9</em> are known to cause Disorders of Sex Development (DSD) and skeletal malformations such as campomelic dysplasia.</div></div><div><h3>Objective</h3><div>This study aimed to analyze the structural and functional impact of <em>SOX9</em> mutations identified in DSD patients, using in silico predictive tools including IntFOLD, to evaluate changes in protein conformation and correlate them with observed phenotypes.</div></div><div><h3>Methods</h3><div>Twenty-eight patients with DSD (46,XX or 46,XY karyotypes) were enrolled. The <em>SRY</em> and <em>SOX9</em> genes were amplified by PCR and sequenced. Four 46,XX patients were found to be <em>SRY</em>-positive, and two 46,XY patients were <em>SRY</em>-negative. Ten <em>SOX9</em> variants were identified in 12 patients, including two novel intronic variants, two in the 3′UTR region, three synonymous, and three non-synonymous coding variants. All variants were found in the heterozygous state, and the presence of a normal allele was used to assess its functional implications.</div></div><div><h3>Results</h3><div>Non-synonymous mutations located within the <em>HMG</em> and <em>dimerization domains</em> were predicted to be deleterious. 3D modeling using IntFOLD revealed conformational changes, altered protein stability, and disrupted ligand-binding residues. These structural alterations correlated with the DSD phenotypes observed. The overall <em>SOX9</em> structure showed a largely disordered organization, with ordered segments within key functional domains.</div></div><div><h3>Conclusion</h3><div>Our findings confirm the role of <em>SOX9</em> in the etiology of DSD and highlight the relevance of structural modeling for interpreting rare variants. The integration of clinical, genetic, and in silico data contributes to a better understanding of sex differentiation mechanisms and may support improved molecular diagnosis of DSD.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201461"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144831345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and molecular insights into diabetic foot ulcers: Unveiling biomarkers for precision medicine","authors":"Ratanjeet Singh Sudan,&nbsp;Priyanka Garg,&nbsp;Palakurthi Yanadaiah","doi":"10.1016/j.humgen.2025.201500","DOIUrl":"10.1016/j.humgen.2025.201500","url":null,"abstract":"<div><div>Diabetic foot ulcers (DFUs) are a prominent and serious outcome of diabetes that can have a major impact on quality of life. Diabetic foot ulcers (DFUs) exhibit a delayed recovery owing to the physiological healing cascade. The typical wound healing process, which encompasses angiogenesis, inflammation, and extracellular matrix (ECM) remodeling, is disrupted and inhibited in diabetic foot ulcers (DFUs). Upon injury to the tissue, neutrophils and monocytes migrate to the site of injury and secrete reactive oxygen species (ROS), matrix metalloproteinase (MMP)-8. In addition to that, the other biomarkers like procalcitonin, pentraxin-3, C-reactive protein (CRP), interleukins (ILs), and tumor necrosis factor-α (TNF-α), are secreted as an inflammatory response. These inflammatory mediators play a significant role as novel biomarkers reflecting the impact of therapeutic interventions. Numerous studies state that, single nucleotide variants (SNVs) in multiple genes may contribute to abnormal inflammatory response leading to the delayed healing of diabetic foot ulcers (DFUs). This article summarizes current information on the generation of diabetic foot ulcers (DFUs) concerning single-nucleotide variants (SNVs). This review unveils a comprehensive summary of emerging biomarkers and single-nucleotide variants (SNVs) that facilitate accurate diagnosis and risk assessment of diabetic foot ulcers (DFUs).</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201500"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145415619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic, transcriptomics, and epigenomic alterations in AREG gene in LUSC and HNSCC","authors":"K. Akshaya Krishnan ,&nbsp;P. Anitha ,&nbsp;J. Vijayashree Priyadharsini ,&nbsp;A. Paramasivam","doi":"10.1016/j.humgen.2025.201477","DOIUrl":"10.1016/j.humgen.2025.201477","url":null,"abstract":"<div><h3>Objectives</h3><div>Cancers of the head and neck region and lungs share similar risk factors. The increased prevalence of these two cancer types underscores the need to identify diagnostic, therapeutic, and prognostic biomarkers for their management. In this context, the present study aims to identify genetic alterations in the <em>AREG</em> gene and their possible association with HNSCC and LUSC.</div></div><div><h3>Methods</h3><div>The study employed a computational design, utilizing the following databases and tools to identify the association between disease phenotypes and genes. The cBioPortal database was used to analyze genetic alterations in the <em>AREG</em> gene across TCGA datasets for HNSCC and LUSC. The survival probability and gene expression profile were analyzed using UALCAN. Welch's test demonstrated the statistical significance between the normal and tumor tissues. The microRNA targets of <em>AREG</em> were assessed using the miRDB.</div></div><div><h3>Results</h3><div>The <em>AREG</em> gene presented with less than 1 % alteration in HNSCC and 4 % in LUSC. Interestingly, a significant upregulation of <em>the AREG</em> gene was observed in HNSCC patients, whereas downregulation was noted in LUSC. The increased gene expression profile correlated well with a poor prognosis in HNSCC patients, while low expression was associated with a good prognosis in LUSC patients. Experimental validation of OSCC samples revealed a decrease in gene expression compared to normal samples. Furthermore, the microRNAs <em>hsa-miR-1185-1</em> and <em>hsa-miR-487b</em> were identified as potential targets of <em>AREG</em>, influencing the survival of patients with HNSCC.</div></div><div><h3>Conclusions</h3><div>The overexpression of <em>AREG</em> in HNSCC, along with its poor prognosis, highlights the oncogenic role played by this gene. Interestingly, the epigenetic component, specifically microRNAs <em>hsa-miR-1185-1</em> and <em>hsa-miR-487b</em>, was found to be downregulated, suggesting their influence on AREG expression. These findings require further validation through functional studies to elucidate the association between AREG and the cancer phenotype.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201477"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early-onset nephrolithiasis and persistent microscopic hematuria in a child with a novel pathogenic COL4A5 variant in Alport syndrome: A case report and literature review","authors":"Firoz Ahmad ,&nbsp;Niladri Bose ,&nbsp;Alec Correa ,&nbsp;Sapna Sandal ,&nbsp;Mukesh Kumar ,&nbsp;Akashi Vyas ,&nbsp;Amisha Shah ,&nbsp;Meenu Angi ,&nbsp;Jigar Suthar ,&nbsp;Pooja Chaudhary ,&nbsp;Anindyajit Banerjee ,&nbsp;Spandan Chaudhary ,&nbsp;Neeraj Arora","doi":"10.1016/j.humgen.2025.201483","DOIUrl":"10.1016/j.humgen.2025.201483","url":null,"abstract":"<div><div>A 4-year-old male with persistent microscopic hematuria, hypocalciuria along with hypocitraturia. Renal ultrasound revealed bilateral microcalculi without structural anomalies. Ophthalmic and auditory evaluations were unremarkable. Family history indicated renal disease in the maternal aunt and maternal microscopic hematuria. Whole-exome sequencing (WES) identified a novel hemizygous nonsense variant in <em>COL4A5</em> (NM_033380.3: c.1555C &gt; T; p.Gln519*), truncating the protein at codon 519 of 1770. The variant, inherited from the mildly symptomatic mother (microscopic hematuria, right renal cyst), was absent in population databases and classified as pathogenic based on ACMG criteria (PVS1_Strong, PM2_Supporting, PP1_Supporting, PP4_Supporting). CytoScan 750 K array ruled out copy-number variations. This case expands the genotypic spectrum of Alport syndrome (AS), demonstrating an early presentation with nephrolithiasis, and underscores the diagnostic utility of WES in atypical inherited nephropathies.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201483"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of TBXA2R, TGF-β1 and Il-18 gene polymorphisms in the pathogenesis of pollen induced allergic asthma- a case-control study from West Bengal, India","authors":"Priti Mondal ,&nbsp;Indranil Ganai ,&nbsp;Himani Biswas ,&nbsp;Saibal Moitra ,&nbsp;Sanjoy Podder","doi":"10.1016/j.humgen.2025.201485","DOIUrl":"10.1016/j.humgen.2025.201485","url":null,"abstract":"<div><h3>Background</h3><div>Allergic asthma is a chronic inflammatory disease of the respiratory system's conducting airways affecting 330 million people globally and causes intermittent attacks of breathlessness, wheezing, airway hyper-reactivity and coughing when exposed to specific allergens. Thromboxane A2 receptor (TBXA2R), Transforming Growth Factor Beta 1 (TGF-β1) and Interleukin-18 (IL-18) genes are reported to be involved in inflammatory and immune response pathways related to asthma. Based on the above facts it can be hypothesized that single nucleotide polymorphisms (SNPs) in these genes may be associated with the asthma phenotype.</div></div><div><h3>Objectives</h3><div>The present study aims to analyze the role of the TBXA2R rs4523, TGF-β1 rs1800470, IL-18 rs1946519, IL-18 rs1946518 and IL-18 rs549908 gene polymorphism in asthma susceptibility among the population of West Bengal, India.</div></div><div><h3>Results</h3><div>Maximum number of patients showed sensitivity towards <em>Azadirachta indica</em> (73.46 %), followed by <em>Cocos nucifera</em> (72.27 %), <em>Caesalpinia pulcherrima</em> (65.17 %), etc. Significant difference in genotype and allele frequencies was obtained between the study groups for TBXA2R rs4523 and IL-18 rs1946519 polymorphisms. Asthma patients possessed significantly higher frequency of TBXA2R rs4523 CC and IL-18 rs1946519 TT genotypes than controls. TBXA2R rs4523 CC and IL-18 rs1946519 TT genotype bearing patients showed highest intensity of SPT reactions. Patients bearing rs4523 CC and rs1946519 TT genotypes had significantly higher FEV1/FVC ratio, total IgE level and blood Eosinophil count than heterozygous or major genotype bearers.</div></div><div><h3>Conclusion</h3><div>The present study concluded that TBXA2R rs4523 and IL-18 rs1946519 polymorphisms are associated with allergic asthma susceptibility in the population of West Bengal, India.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201485"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical, genetic, and bioinformatics analysis of a novel TANGO2 mutation (c.263G > A) in an Iranian Azeri Turkish child with lethal metabolic encephalopathy","authors":"Elnaz Akbari ,&nbsp;Asal Asghari Sarfaraz ,&nbsp;Mortaza Bonyadi ,&nbsp;Mohammad Barzegar","doi":"10.1016/j.humgen.2025.201478","DOIUrl":"10.1016/j.humgen.2025.201478","url":null,"abstract":"<div><div>TANGO2-related disorder exhibits significant genotypic and phenotypic heterogeneity, and the clinical significance of novel variants often requires confirmation through detailed case reporting. This case report describes a female child born to consanguineous parents with an unremarkable prenatal and perinatal history. Initial development was normal, but by the second year of life, she exhibited developmental regression, and seizures, which were controlled with levetiracetam. At age 5, she presented with acute encephalopathy, dark urine, rhabdomyolysis, hypoglycemia, and hyperammonemia following a febrile illness. Whole-exome sequencing (WES) identified a novel homozygous <em>TANGO2</em> variant (c.263G &gt; A, p.Arg88Gln), confirmed via Sanger sequencing, with both parents being heterozygous carriers. Bioinformatics analysis predicted pathogenic effects, including potential exon skipping and protein structural alterations. The variant was absent in 430 ethnically matched controls and major population databases (gnomAD, 1000 Genomes), supporting its pathogenicity. Despite management, the patient experienced recurrent metabolic crises and ultimately succumbed to severe rhabdomyolysis and renal failure at age 8. This case underscores the severe phenotypic consequences of biallelic <em>TANGO2</em> mutations, including developmental delay, metabolic instability, and early mortality, while highlighting the importance of genetic diagnosis in unexplained pediatric encephalopathies.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201478"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145057241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}