Genes & genomics最新文献

{"title":"Multi-target mechanisms of Creatine in Parkinson's disease: an in-silico and in-vivo investigation.","authors":"Sneha Kispotta, Vishal Singh, Pratap Kumar Sahu, Utkalika Sahoo, Monalisa Rout, Kiran Anjum Jew, Alok Kumar, Shakti Ketan Prusty, Debajyoti Das","doi":"10.1007/s13258-025-01695-y","DOIUrl":"10.1007/s13258-025-01695-y","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) is a progressive neurodegenerative disorder marked by the loss of dopaminergic neurons, resulting in impaired motor control and cognitive decline. Despite current therapies, there remains a need for more effective and multifaceted treatment strategies.</p><p><strong>Objective: </strong>This study explores the neuroprotective potential of exogenous Creatine in a Haloperidol-induced PD rat model, with a focus on reducing elevated homocysteine levels and targeting key proteins involved in PD pathology.</p><p><strong>Method: </strong>We proposed a multitarget therapeutic approach, aiming to inhibit ADORA2A, alpha-synuclein, and monoamine Oxidase B (MAO-B) using the same bioactive compound. RNA-seq data from publicly available datasets (BioProject: PRJNA608432; GEO: GSE145814) were analyzed to identify dysregulated proteins and pathways associated with neuroactive ligand-receptor interaction, olfactory transduction, and phototransduction. Using computational methods, including RNA Seq analysis, molecular docking, MMGBSA, and ADME/T analyses, we screened for potential common ligand. Creatine showed a higher binding affinity for the target proteins compared to Levodopa (primarily used medication against PD), suggesting its therapeutic potential. In vivo experiments assessed the efficacy of Creatine through behavioural testing, redox status evaluation, biochemical markers, and histological analysis.</p><p><strong>Result: </strong>The results potentially suggest that Creatine ameliorates motor deficits, reduces oxidative stress, and protects neuronal integrity in PD rats. Overall, our findings indicate that Creatine acts as a promising multitargeted approach, capable of modulating several PD-associated molecular mechanisms.</p><p><strong>Conclusion: </strong>This approach may further be validated and pave the way for more effective, broad-spectrum treatments for Parkinson's disease, addressing both its motor and non-motor symptoms.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"349-368"},"PeriodicalIF":2.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics analysis identifies SMPD1 as a key contributor in sphingolipid pathway for Type 2 diabetes pathogenesis.","authors":"Aron Park, Baeki E Kang, Eun-Ju Jin, Hyun Jin Kim, Chang-Woo Lee, Jae Myoung Suh, Dongryeol Ryu, Seungyoon Nam","doi":"10.1007/s13258-025-01727-7","DOIUrl":"10.1007/s13258-025-01727-7","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes (T2D) is a complex and heterogeneous metabolic disorder that presents significant challenges in treatment development. Emerging evidence indicates that T2D is closely associated with dysregulation of the sphingolipid metabolic pathway, which plays crucial roles in cellular signaling, membrane structure, and metabolic homeostasis.</p><p><strong>Objective: </strong>To identify and characterize key sphingolipid pathway components that contribute to the pathogenesis of T2D.</p><p><strong>Methods: </strong>We employed a multi-omics approach integrating genomic, transcriptomic, and metabolomic datasets. Two-sample Mendelian randomization analysis was performed using genome-wide association study data. For functional validation, we conducted in vivo experiments using both lean and ob/ob mice treated with recombinant sphingomyelin phosphodiesterase 1 (SMPD1).</p><p><strong>Results: </strong>A mouse phenome-liver transcriptome analysis initially identified SMPD1, which converts sphingomyelin to ceramide, as a potential significant factor in T2D. Further investigation using human T2D blood lipid metabolome revealed a decrease of sphingomyelin in T2D patients, strongly suggesting SMPD1's involvement. Two-sample Mendelian randomization, utilizing genome-wide association studies, established a causal effect between SMPD1 gene expression and diabetic traits. Additionally, bulk and single-cell RNA-seq datasets from liver tissues with metabolic dysfunction-associated steatotic liver disease (MASLD) showed that SMPD1 was upregulated in MASLD hepatocytes. Critically, administering recombinant SMPD1 to both lean and ob/ob mice increased hepatic ceramide levels and worsened glucose intolerance and insulin resistance, definitively confirming SMPD1's pathogenic role.</p><p><strong>Conclusion: </strong>Our findings strongly indicate that SMPD1, as part of the sphingolipid pathway, represents a promising therapeutic target for both T2D and MASLD.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"369-381"},"PeriodicalIF":2.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145804372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the molecular landscape of hepatopancreatic necrosis disease in Eriocheir sinensis using RNA-Seq meta-analysis.","authors":"Adeel Malik, Nitin Mahajan, Hyung-Eun An, Chang-Bae Kim","doi":"10.1007/s13258-025-01715-x","DOIUrl":"10.1007/s13258-025-01715-x","url":null,"abstract":"<p><strong>Background: </strong>The Chinese mitten crab (Eriocheir sinensis) is a commercially important crustacean, highly valued in China and Korean peninsula for its nutritional benefits and delicate flavor. However, the aquaculture industry has been significantly impacted by hepatopancreatic necrosis disease (HPND), leading to substantial economic losses. The exact cause and molecular mechanisms underlying HPND remain poorly understood.</p><p><strong>Objective: </strong>This study aimed to decipher the genetic and molecular basis of HPND through an integrative transcriptomic meta-analysis to identity consistent and disease related gene expression patterns.</p><p><strong>Methods: </strong>Publicly available RNA-Seq datasets from three different studies were systematically integrated and analyzed. Differentially expressed transcripts (DETs) were identified through meta-analysis, followed by functional annotation and enrichment analyses of Gene Ontology and KEGG pathways.</p><p><strong>Results: </strong>The meta-analysis identified 571 DETs, including 245 up-regulated and 326 down-regulated transcripts in diseased hepatopancreas. Functional enrichment revealed significant disruptions in the pathways of protein modification, lipid metabolism, and vesicle-mediated transport. These processes are crucial for immune functions including pathogen detection, antigen presentation, cytokine secretion, and metabolic adaptation to stress in the hepatopancreas. Moreover, we found 11 novel DETs (6 up-regulated and 5 down-regulated), highlighting the ability of meta-analysis to uncover low-abundance or context-specific genes that may escape detection in individual studies.</p><p><strong>Conclusions: </strong>Our study provides valuable insights into the causes and pathogenic mechanisms of HPND, identifies novel genetic factors and gene markers for detection, and offers a deeper understanding of the disease, highlighting potential biomarkers for its prevention in E. sinensis aquaculture.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"253-270"},"PeriodicalIF":2.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145603760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular remodeling of the central auditory pathway in tinnitus revealed by RNA sequencing.","authors":"Ha Hyun Song, Byeonghyeon Lee, Hyeon Joon Shin, Ye-Ri Kim, Subi Ham, Un-Kyung Kim, Incheol Seo, Da Jung Jung","doi":"10.1007/s13258-025-01718-8","DOIUrl":"10.1007/s13258-025-01718-8","url":null,"abstract":"<p><strong>Background: </strong>Tinnitus is a complex neurological condition affecting 10-15% of adults worldwide, characterized by phantom auditory perception without external sound sources. While traditional investigations have focused on discrete auditory structures, emerging evidence suggests tinnitus involves broader alterations across central auditory regions.</p><p><strong>Objective: </strong>This study employed transcriptomic analysis to investigate molecular mechanisms underlying salicylate-induced tinnitus across multiple brain regions simultaneously.</p><p><strong>Methods: </strong>Male C57BL/6 N mice received daily intraperitoneal injections of sodium salicylate (350 mg/kg) for five consecutive days to induce tinnitus-like behavior, assessed using gap-prepulse inhibition of acoustic startle reflex. RNA sequencing was performed on auditory cortex, inferior colliculus, and cochlear nucleus tissues. Differential gene expression analysis, weighted gene co-expression network analysis, and functional annotation were conducted to identify shared molecular signatures and pathways across auditory centers.</p><p><strong>Results: </strong>Principal component analysis revealed region-specific transcriptomic changes following salicylate treatment. Differential gene expression analysis identified Depp1 and Angptl4 as consistently upregulated genes across multiple brain regions, particularly within the inferior colliculus and cochlear nucleus. Weighted gene co-expression network analysis revealed a 215-gene module increased across all auditory regions in tinnitus mice, with functional annotation indicating enrichment for vasculature-related biological processes. Depp1 emerged as a central hub gene linking oxidative stress responses to autophagy mechanisms.</p><p><strong>Conclusion: </strong>This study shows that tinnitus pathology involves not only neuronal hyperactivity but also oxidative stress, neuroinflammation, and autophagy in the central auditory pathway. Depp1 acts as a molecular hub linking redox imbalance to cellular clearance, highlighting its potential as a therapeutic target and offering new insights for intervention.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"317-325"},"PeriodicalIF":2.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor microenvironment-driven drug resistance in urologic cancers: mechanisms and therapeutic targets.","authors":"Gi-Eun Yang, Seo-Yeong Yoon, Ju-Seog Lee, Sun-Hee Leem, Yung-Hyun Choi","doi":"10.1007/s13258-025-01710-2","DOIUrl":"10.1007/s13258-025-01710-2","url":null,"abstract":"<p><p>Therapeutic resistance remains a major challenge in the management of urologic cancers, including renal cell carcinoma (RCC), bladder cancer (BC), and prostate cancer (PCa). Recent advances highlight the tumor microenvironment (TME) as a critical determinant of treatment failure across various modalities, such as androgen deprivation therapy (ADT), VEGF-targeted therapies, and immune checkpoint inhibitors (ICIs). This review summarizes how distinct TME components-such as cancer-associated fibroblasts (CAFs), extracellular matrix (ECM), immunosuppressive cells, and hypoxic conditions-promote resistance. CAFs drive oncogenic reactivation and epithelial-mesenchymal transition (EMT), while ECM stiffening hinders immune infiltration and facilitates pro-survival signaling. Immune evasion mechanisms include TGF-β-mediated T cell exclusion, regulatory T cell expansion, and adaptive checkpoint upregulation. Hypoxia and metabolic reprogramming further promote cancer stemness and immune suppression through HIF-2α activation, lactate accumulation, and acidification of TME. Targeting these resistance mechanisms requires a multifaceted approach. Promising strategies include ICI combination therapies with anti-angiogenics or TGF-β inhibitors, ECM-modulating agents, and hypoxia-targeted drugs. Novel approaches such as single-cell and spatial transcriptomics, organoid co-culture systems, and TME-derived biomarkers offer new opportunities for patient stratification and therapeutic development. Integrating TME biology into clinical practice is essential to overcome resistance and improve outcomes in urologic oncology.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"173-184"},"PeriodicalIF":2.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145603505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conservation and diversity of genes expressed in the spines of the sea urchin.","authors":"August Guang, Cosmo Pieplow, Gary M Wessel","doi":"10.1007/s13258-025-01703-1","DOIUrl":"10.1007/s13258-025-01703-1","url":null,"abstract":"<p><strong>Background: </strong>Echinoids, known as sea urchins, are a benthic family of marine invertebrates named for their spiny projections. Echinodermata translates from Greek to \"Spiny Skin,\" yet in the laboratory setting, it is the embryos, not the spines, of these animals that are subjected to a wealth of molecular analyses.</p><p><strong>Objective: </strong>In this study, we test the identity of genes expressed in the spines and identify conservation between four distant species.</p><p><strong>Methods: </strong>We generated several transcriptomes de novo from four selected sea urchin species with a great diversity in size, color, and shape, representing 255 MYA of evolution (Strongylocentrotus purpuratus, Hemicentrotus pulcherrimus, Lytechinus variegatus, Eucidaris tribuloides). From de novo spine transcriptomes, we test for orthologous gene families, generating a wealth of orthogroups, as well as a species tree constructed from the available transcripts of only the spine.</p><p><strong>Results: </strong>Core families of transcripts shared between all species, reveal that pathways involved in cell surface antigen-recognition, protein turnover, and cytoskeletal structure are each shared by diverse species of Echinoids. A basal branching species, Eucidaris tribuloides, contained a large number of unique transcripts, reflecting its unique spine morphology. When the spine transcriptome from Lytechinus variegatus was depleted of transcripts expressed elsewhere from the adult sea urchin, the resulting enriched spine transcriptomes were used for Orthofinder analysis, DEG analysis, and GO pathway analysis.</p><p><strong>Conclusion: </strong>Regardless of species, the spines are an organ with an abundance of gene expression for sensory, structural, and defense functions, well attuned to its habitat in the benthos.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"185-199"},"PeriodicalIF":2.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145400618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antarctic soil microbiomes as a reservoir for cosmetic bioactives: continental-scale diversity and predicted functions.","authors":"Giuk Gim, Dong-Geol Lee, Chun Ho Park, Ok-Sun Kim, Kyudong Han, Young Mok Heo, Hanbyul Lee","doi":"10.1007/s13258-025-01721-z","DOIUrl":"10.1007/s13258-025-01721-z","url":null,"abstract":"<p><strong>Background: </strong>Demand for clean beauty ingredients is driving discovery of safe, effective, and sustainable actives. Microbes inhabiting polar deserts produce biomolecules adapted to stress, relevant to skin protection and regeneration.</p><p><strong>Objective: </strong>To characterize taxonomic diversity and functional potential of Antarctic soil microbiomes from distinct biogeographic regions and identify microbial genes linked to cosmetic efficacy.</p><p><strong>Methods: </strong>Public 16S rRNA amplicon datasets from NCBI SRA were compiled and classified into four Antarctic Conservation Biogeographic Regions: North Antarctic Peninsula, East Antarctica, South Victoria Land, and Transantarctic Mountains. Functional profiles were predicted using PICRUSt2 and analyzed for antioxidant, anti-aging, moisturization, skin-barrier, and regeneration pathways via KEGG Orthology terms.</p><p><strong>Results: </strong>Analysis of 406 sequencing runs identified 54,523 amplicon sequence variants from 48 bacterial and 2 archaeal phyla. Actinobacteria dominated (36.1%), followed by Bacteroidetes (13.0%) and Proteobacteria (10.5%). East Antarctica exhibited highest diversity (Shannon index mean 8.97) and evenness (0.87), with region-distinct communities. Functional prediction revealed enriched antioxidant defense, skin-barrier maintenance, moisturization, and photoprotective genes. Taxonomic and functional ordinations partially decoupled, indicating functional convergence amid taxonomic divergence.</p><p><strong>Conclusion: </strong>Antarctic soils are a rich source of microbial functions for cosmetic innovation, especially in East Antarctica. Multi-omics validation, strain isolation, and sustainable production may accelerate development of next-generation clean beauty actives compliant with access and benefit-sharing regulations.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"305-315"},"PeriodicalIF":2.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA-124 induces AML differentiation and apoptosis through c-Myc suppression.","authors":"Byeol-Eun Jeon, Chan-Seong Kwon, Ji-Eun Lee, Su-Ji Lee, Kwonwoo Song, Yun Ju Lee, Du Hyeong Lee, Sang-Woo Kim","doi":"10.1007/s13258-025-01714-y","DOIUrl":"10.1007/s13258-025-01714-y","url":null,"abstract":"<p><strong>Background: </strong>Acute myeloid leukemia (AML) is a hematologic malignancy marked by blocked differentiation and uncontrolled proliferation. While miR-124 has been implicated as a tumor suppressor in various cancers, its functional role in AML remains unclear.</p><p><strong>Objective: </strong>This study aimed to investigate the anti-leukemic effects of miR-124 and its regulatory mechanisms involving c-Myc and ROS signaling in AML.</p><p><strong>Methods: </strong>AML cells were engineered to overexpress miR-124. Functional assays including flow cytometry, viability, and apoptosis analyses were conducted. ROS levels were measured, and c-Myc regulation was evaluated via western blotting, qPCR, ChIP, and pharmacological inhibition. Exosome-mediated delivery was also examined.</p><p><strong>Results: </strong>miR-124 overexpression induced AML cell differentiation and apoptosis, accompanied by ROS accumulation and c-Myc downregulation. ROS induction suppressed c-Myc and activated the p21/p16/Rb axis, promoting cell cycle arrest. ChIP assays revealed that c-Myc binds the miR-124 promoter, indicating a negative feedback loop. Combination treatment with miR-124 and a c-Myc inhibitor enhanced anti-proliferative effects. Additionally, miR-124-containing exosomes reduced AML cell viability.</p><p><strong>Conclusions: </strong>miR-124 acts as a tumor suppressor in AML by modulating a ROS-dependent c-Myc signaling pathway and inducing differentiation and apoptosis. These findings highlight miR-124 as a promising therapeutic and prognostic target in AML.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"237-251"},"PeriodicalIF":2.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145603520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide association study of quantitative ocular traits, including axial length and central corneal thickness, identifies loci for refractive error in the Korean population.","authors":"Woo Young Lim, Kui Dong Kang, Yoon Shin Cho","doi":"10.1007/s13258-025-01719-7","DOIUrl":"10.1007/s13258-025-01719-7","url":null,"abstract":"<p><strong>Background: </strong>The eye is a sensory organ that receives light and generates visual information. Refractive errors, which are influenced by both genetic and environmental factors, are a major cause of visual impairment. In particular, the high prevalence of myopia in some East Asian countries has become an increasing public health concern.</p><p><strong>Objective: </strong>To gain insights into the genetic basis of refractive error, this study aimed to identify genetic associations for axial length (AL) and central corneal thickness (CCT), two quantitative ocular traits that contribute to refractive error.</p><p><strong>Methods: </strong>We conducted genome-wide association (GWA) analyses of 649 Korean individuals using the Korea Biobank Array (KBA) chip to identify genetic variants associated with AL and CCT. After SNP imputation, a total of 9,408,715 common SNPs were included in the association analysis. Additionally, 97,434 rare variants were analyzed using q.emmax test. Gene-based analyses were further performed to detect genes significantly associated with these ocular traits.</p><p><strong>Results: </strong>The GWA analyses identified 10 common variants (minor allele frequency [MAF] ≥ 1%) significantly associated with AL and 2 with CCT (P < 5 × 10⁻⁸). Analyses of rare variants (MAF < 1%) further detected 7 associations with AL and 2 with CCT. In addition, gene-based analysis identified MROH1 as significantly associated with AL.</p><p><strong>Conclusion: </strong>This study identified novel genetic associations influencing AL and CCT in the Korean population. These findings provide new insights into the genetic architecture of refractive error and may contribute to improving eye health through the prediction of genetic predisposition to refractive errors.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"293-303"},"PeriodicalIF":2.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145668164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel duplication mutation in the MYO7A gene associated with autosomal recessive hearing loss in a Chinese family.","authors":"Jie Li, Shengmei Yang, Mina Xiang, Qingling An, Yuannan Wu, Qingli Quan, Haiou Jiang","doi":"10.1007/s13258-025-01716-w","DOIUrl":"10.1007/s13258-025-01716-w","url":null,"abstract":"<p><p>BACKGROUND: Hearing loss (HL) is one of the most common sensory defects with genetic and environmental etiologies, which is classified into syndromic and non-syndromic hearing loss (NSHL). Variants in MYO7A have been found to result in non-syndromic hearing loss (DFNB2, DFNA11) and Usher Syndrome type 1B (USH1B). However, only a small number of variants result in DFNB2. OBJECTIVE: To explore the pathogenic variant for a Chinese pedigree with autosomal recessive hearing loss (ARNSHL). METHODS: The clinical characteristics of the Chinese family were mainly showed by the audiological and ocular examinations. Exome sequencing and Sanger sequencing were utilized to identify the causative variant of the Chinese pedigree with ARNSHL, followed by molecular modeling analysis of effect of the variant on the protein function. RESULTS: The affected patients currently simply exhibited symmetrical bilateral severe-to-profound neurosensory deafness at all frequencies without vestibular dysfunction or retinitis pigmentosa. We identified a novel duplication variant c.275_278dupACCT in the MYO7A gene using exome sequencing, which was further confirmed by Sanger sequencing. This homozygous variant was co-segregated with the ARNSHL phenotype in this Chinese family. Genetic mutation analysis and molecular modeling function prediction further supported the hypothesis that this novel homozygous variant is pathogenic. CONCLUSION: The novel homozygous variant c.275_278dupACCT (p.Ile94Profs*47) in MYO7A gene is responsible for this Chinese family with ARNSHL. Our results expand the spectrum of MYO7A variants and provide molecular insights into the pathogenesis of NSHL.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"285-291"},"PeriodicalIF":2.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145699864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}