Journal of Applied Genetics最新文献

{"title":"MiR-1976 affects lung squamous cell carcinoma development by targeting NCAPH.","authors":"Yan Li, Hongwei Zhou, Yibing Yao, Zaiwen Fan","doi":"10.1007/s13353-025-00990-4","DOIUrl":"10.1007/s13353-025-00990-4","url":null,"abstract":"<p><p>Lung squamous cell carcinoma (LUSC) is one of the major subtypes of lung cancer. Non-SMC condensin I complex subunit H (NCAPH) is highly regarded as a valuable biomarker in certain malignant tumors. However, the specific roles of NCAPH in LUSC are not well understood. The objective of this work was to determine the effect of NCAPH on the progression of LUSC and to identify the microRNAs (miRNAs) located upstream of NCAPH that regulate its function. MicroRNA and mRNA expression profiles, as well as clinical data of LUSC (Normal: 49, LUSC: 502), were obtained from the TCGA database for the purpose of differential analysis and survival analysis. The expression of NCAPH and miR-1976 in LUSC cell lines was detected using Quantitative reverse transcription PCR (qRT-PCR) and western blot techniques. In this study, the impact of NCAPH on the proliferation of LUSC cells was assessed using CCK-8 and colony formation assay. Additionally, the effects of NCAPH on the migration and invasion of LUSC cells were evaluated using the Transwell assay. Furthermore, the effects of NCAPH on the apoptosis of LUSC cells were evaluated using flow cytometry. The target miRNAs of NCAPH were predicted using bioinformatics, and the targeting link between miR-1976 and NCAPH was confirmed using a dual-luciferase reporter gene experiment. The findings indicated that the expression of NCAPH was notably elevated in LUSC tissues (P < 0.05), while the expression of its upstream miRNA (miR-1976) was notably reduced (P < 0.05). The dual-luciferase test results indicated that miR-1976 functions as an upstream target miRNA of NCAPH. Low expression of NCAPH may inhibit the proliferation (P < 0.05), migration (P < 0.05), invasion (P < 0.05), and promote apoptosis (P < 0.05) in LUSC cells. However, the suppression of miR-1976 may reverse this inhibitory effect by specifically targeting NCAPH. This study showed that NCAPH can serves as a novel potential oncogenic biomarker for LUSC and its regulation is controlled by upstream miR-1976. miR-1976 can directly targets NCAPH to affect the proliferation, migration, invasion, and apoptosis of LUSC cell.</p>","PeriodicalId":14891,"journal":{"name":"Journal of Applied Genetics","volume":" ","pages":"649-660"},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13534149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative trait loci for Globodera pallida resistance derived from wild potato species Solanum gourlayi.","authors":"Dorota Milczarek, Jadwiga Śliwka, Beata Tatarowska, Anna Podlewska-Przetakiewicz, Jarosław Plich","doi":"10.1007/s13353-025-01023-w","DOIUrl":"10.1007/s13353-025-01023-w","url":null,"abstract":"<p><p>Globodera pallida is a major pest that is responsible for huge losses in potato yields worldwide. Expanding the gene pool of cultivated potatoes with clones resistant to this pest is made possible by searching for resistance genes in wild Solanum species. The aim of this study was to identify quantitative trait loci (QTLs) for potato resistance to Globodera pallida derived from Solanum gourlayi. A resistant diploid potato clone, Sg 2/7 (Solanum gourlayi, accession CGN17592), was crossed with a susceptible potato hybrid clone, DW 94-4235, to generate an F1 mapping population. All clones were tested for nematode resistance using G. pallida, pathotypes Pa2 and Pa3, in 2 or 3 years (2017-2019), respectively. Diversity Array Technology (DArTseq) was used for genotyping and genetic map construction. QTLs for nematode resistance were identified on potato chromosomes II, IV, V, VI, VII, X, XI, and XII, explaining from 10.1 to 21.5% of phenotypic variance. The most significant QTL for resistance to G. pallida pathotype Pa2 was identified on chromosome XII, explaining 20.9% of the phenotypic variance in the dataset from 2017. The most significant QTL for resistance to the G. pallida Pa3 pathotype was identified on chromosome VI, with a CAPS marker Exp928 in its peak, explaining 21.5% of the phenotypic variance in the dataset from 2017. The novel QTLs for resistance to S. gourlayi may be useful for breeding resistant potato cultivars, further studies of candidate genes, and host responses of potato to G. pallida infection.</p>","PeriodicalId":14891,"journal":{"name":"Journal of Applied Genetics","volume":" ","pages":"533-541"},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13534178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145345117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liver response to early embryonic stimulation with xylo-and mannooligosaccharides in broiler chickens.","authors":"Aleksandra Bełdowska, Marcin Barszcz, Anna Tuśnio, Adrianna Konopka, Kamil Gawin, Ewa Święch, Maria Siwek, Aleksandra Dunisławska","doi":"10.1007/s13353-026-01071-w","DOIUrl":"10.1007/s13353-026-01071-w","url":null,"abstract":"<p><p>The gut microbiota plays an important role in signaling between the intestines and the liver. These two organs are connected by a bidirectional relationship known as the gut-liver axis. The aim of this study was to determine the impact of oligosaccharides delivered in ovo on liver physiology in broiler chickens. On the 12th day of incubation, the following substances were injected into the eggs of ROSS 308 broiler chickens: saline (control), xylotriose (XOS3), xylotetrose (XOS4), mannotriose (MOS3) or mannotetrose (MOS4). The dose of oligosaccharides was 0.5 mg/0.2 ml saline. Blood, bile and liver samples were collected post-mortem on day 42. Compared to the other groups, the MOS3 significantly increased the level of uric acid in the blood, while the XOS3, XOS4 and MOS3 groups had a higher magnesium concentration than the control group. All oligosaccharides decreased catalase and total superoxide dismutase activity. Compared to the other groups, the administration of MOS3 and MOS4 increased the content of oxidants in the liver of chickens. XOS4 increased the expression of the ANGPTL4, CYR61, KLHL6, NR4A3 and SYK genes compared to the control group, while MOS3 increased the expression of ANGPTL4, KLHL6 and NR4A3 genes. MOS3 increased and MOS4 decreased the level of DNA methylation for the ANGPTL4 gene. XOS4 and both MOS3 and MOS4 increased the methylation of NR4A3 gene. Therefore, it can be concluded that XOS and MOS decrease antioxidant status of the liver but increased the expression of genes related to the immunity and metabolism.</p>","PeriodicalId":14891,"journal":{"name":"Journal of Applied Genetics","volume":" ","pages":"787-803"},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13534220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148042143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel genomic regions associated with adult-plant resistance to multiple fungal pathogens in wheat (Triticum aestivum L.) revealed by DArT marker sequencing.","authors":"Elżbieta Czembor, Łukasz Stępień, Jerzy H Czembor","doi":"10.1007/s13353-026-01077-4","DOIUrl":"10.1007/s13353-026-01077-4","url":null,"abstract":"<p><p>Wheat is among the top three most important cereal crops globally and serves as a staple food for approximately 40% of the world's population. Fungal leaf diseases such as yellow and leaf rusts (YR, LR), septoria nodorum blotch (SNB), septoria tritici blotch (STB), and powdery mildew (PM) have a major effect on yield loss in wheat, and resistance breeding is so far the most effective strategy to minimize those losses. Adult plant resistance (APR) is a crucial component of durable disease resistance; it reduces the pathogen's infection rate, keeping disease levels below the damage threshold, even in the absence of complete immunity. Therefore, this study aimed to identify sources of resistance in a collection of 411 accessions from diverse global origins. These accessions were phenotyped across 2018-2019. DArTseq technology and Genome-wide association studies (GWAS) analysis were conducted to identify single-nucleotide polymorphisms (SNPs) associated with APR for evaluated pathogens. DArT analysis showed that wheat chromosome 2B contains genomic regions associated with resistance to SNB, and that SNPs on chromosome 3B are associated with resistance to YR. On chromosome 6 A, there is a strong potential to explore, as a shared resistance locus for YR and SNB was found. SNPs: 3,937,236, 1,056,817 were consistent in both years, meaning their association with disease resistance is reliable and repeatable. Chromosome 7D is a strong region for SNPs significantly associated with both LR and SNB resistance. While multiple disease resistance genes are present on 7D, the 610 Mb LR locus is distinct from known LR, PM, and SNB loci, making it a strong candidate for functional validation. These findings highlight the value of historical resistance sources and uncover novel genomic regions for breeding a broad-spectrum APR-based resistance. Dual-trait loci, especially those effective against both biotrophic and necrotrophic pathogens, represent a promising material for achieving durable resistance in elite wheat cultivars.</p>","PeriodicalId":14891,"journal":{"name":"Journal of Applied Genetics","volume":" ","pages":"543-560"},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13534208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148251665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular interplay of lncRNAs, miRNAs, and mRNAs axes in triple-negative breast cancer: implications for metastatic progression.","authors":"Deepshikha Rathore, Ishita Agarwal, Smit Patel, Nishita Adnani, Nandani Dharwal, Nirali Shukla, Heena V Dave","doi":"10.1007/s13353-026-01061-y","DOIUrl":"10.1007/s13353-026-01061-y","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) constitutes 15-17% of all breast cancer cases. The absence of molecular targets restricts targeted therapy options for TNBC. Despite the availability of conventional chemotherapy, high recurrence rates and metastasis remain the primary challenges in current disease management. Nearly 46% of TNBC cases are metastasized to distant organs, which decreases the overall survival of TNBC patients. Therefore, identifying disease-specific markers, their mechanisms in metastasis, and their therapeutic potential could aid in developing better treatment options for patients. Long non-coding RNAs (lncRNAs), a subset of non-coding RNAs (> 200 nucleotides), exhibit significant function in gene expression regulation and tumorigenesis. LncRNAs play a significant role in TNBC metastasis through diverse mechanisms. LncRNAs such as H19, MALAT1, and others contribute to TNBC chemotherapy resistance, invasion, migration, relapse, and immune suppression. Furthermore, the molecular interactions among lncRNAs, miRNAs, and mRNAs collectively drive key hallmarks of metastatic progression, specifically in TNBC. To provide a comprehensive understanding of these mechanisms, this review highlights the biogenesis, classification, and physiological functions of lncRNAs, along with an overview of the metastatic cascade. Specifically, it emphasizes the regulatory axes of lncRNAs with miRNAs and mRNAs in driving metastatic progression, and explores their emerging role as promising biomarkers for diagnosis and targeted therapy. Expanding the understanding of lncRNA-mediated regulatory interactions could pave the way for the identification of novel biomarkers and the development of more effective therapeutic strategies to enhance TNBC diagnosis, prognosis, and treatment outcomes.</p>","PeriodicalId":14891,"journal":{"name":"Journal of Applied Genetics","volume":" ","pages":"617-629"},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NGS sequencing reveals the cause of hearing loss in a group of Polish patients with an isolated, non-DFNB1 hearing loss.","authors":"Katarzyna Niepokój, Agnieszka Magdalena Rygiel, Katarzyna Wertheim-Tysarowska, Justyna Sawicka, Barbara Dorożko, Alicja Grabarczyk, Ewa Obersztyn, Anna Kutkowska-Kaźmierczak, Jakub Klapecki, Artur Barczyk, Paweł Własienko, Piotr Jurczak, Aneta Lebiedzińska, Robert Śmigiel, Aleksandra Jakubiak, Jolanta Wierzba, Ewa Kaczorowska, Aleksandra Pietrzyk, Grażyna Sorbaj-Sucharska, Janusz Limon, Jerzy Bal","doi":"10.1007/s13353-025-00991-3","DOIUrl":"10.1007/s13353-025-00991-3","url":null,"abstract":"<p><p>The etiology of hearing loss (HL) is heterogeneous. It is estimated that 50-60% of the cases have a genetic background, with the other part being environmental. Isolated HL is responsible for nearly two-thirds of congenital cases, and the remaining part accounts for syndromic forms (SHL). The study aim was to examine the molecular basis of HL in 48 Polish patients with isolated, non-DFNB1 hearing loss using the targeted next-generation sequencing technique (NGS). The molecular cause of the HL was defined in 39.6% (19/48) of patients. In thirteen genes, we identified causative variants, including six novel ones: p.Gly1326Val (STRC), p.Pro104ThrfsTer2 (MYO6), p.Tyr186Ter (GATA3), p.Ile1584SerfsTer12 (MYO15A), p.Pro559Leu, and p.Glu542del (CDH23). The pathogenic status of novel variants was assessed by using bioinformatic tools and the ACMG recommendations. The most frequent genetic variants were the STRC gene deletions and point variants in Usher syndrome genes. For 36.8% of patients, the molecular diagnosis suggested SHL (Deafness-Infertility Syndrome (DIS), Hypoparathyroidism, Sensorineural Deafness and Renal Disease (HDR), Usher, Perrault and Waardenburg syndromes). The obtained results confirmed the heterogeneity of the molecular basis of HL in Polish patients and the usefulness of the NGS technique as a diagnostic tool.</p>","PeriodicalId":14891,"journal":{"name":"Journal of Applied Genetics","volume":" ","pages":"701-710"},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13534204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Molecular interplay of lncRNAs, miRNAs, and mRNAs axes in triple-negative breast cancer: implications for metastatic progression.","authors":"Deepshikha Rathore, Ishita Agarwal, Smit Patel, Nishita Adnani, Nandani Dharwal, Nirali Shukla, Heena V Dave","doi":"10.1007/s13353-026-01068-5","DOIUrl":"10.1007/s13353-026-01068-5","url":null,"abstract":"","PeriodicalId":14891,"journal":{"name":"Journal of Applied Genetics","volume":" ","pages":"857"},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 identification and characterization of GATA transcription factors in Avena sativa L. and expression profiling under salinity stress.","authors":"Muskan Bokolia, Tanu Singh, Nandni Goyal, Avneesh Kumar, Kashmir Singh, Baljinder Singh","doi":"10.1007/s13353-025-01007-w","DOIUrl":"10.1007/s13353-025-01007-w","url":null,"abstract":"<p><p>GATA transcription factors are a group of type IV zinc-finger proteins that play critical roles in regulating plant growth, development, and responses to abiotic stress. These genes are characterized by a conserved DNA-binding domain with the consensus sequence (A/T)GATA(A/G) and a type IV zinc-finger motif containing the conserved sequence CX2CX18-20CX2C. In this study, 27 GATA genes (designated AsGATA) were identified in Avena sativa using the GrainGenes genome database. Comprehensive analyses were performed to examine their conserved motifs, physicochemical properties, chromosomal localization, gene structures, phylogenetic relationships, and cis-acting regulatory elements. Based on the classification of GATA family members in Arabidopsis thaliana, the AsGATA genes were categorized into four subfamilies. Gene structure analysis revealed that members of the same subfamily generally exhibited similar structural features. Subcellular localization predictions indicated that most AsGATA proteins are Likely to function in the nucleus. Chromosomal mapping demonstrated the random distribution of the 27 AsGATA genes across the 21 chromosomes of Avena sativa. Expression profiling, based on RNA-Seq data from the NCBI SRA database, identified six AsGATA genes that are responsive to salt stress. These genes represent promising candidates for functional studies and could be leveraged in breeding programs to develop salt-tolerant Avena sativa varieties.</p>","PeriodicalId":14891,"journal":{"name":"Journal of Applied Genetics","volume":" ","pages":"513-532"},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of colorectal cancer molecular subtypes and prognostic features based on basement membrane-related genes.","authors":"Leilei Yang, Zhiqing Ji, Yufeng Ren, Chengfeng Fang, Jiaju Han, Dinghai Luo, Ruili Zhang, Shenkang Zhou","doi":"10.1007/s13353-025-00992-2","DOIUrl":"10.1007/s13353-025-00992-2","url":null,"abstract":"<p><p>Recent evidence suggests that the basement membrane (BM) plays an important role in the progression of colorectal cancer (CRC). Here, we investigate the prognostic value of CRC based on BM-associated genes. BM-related differentially expressed genes (DEGs) in CRC were obtained through analysis of The Cancer Genome Atlas public database and literature. The DEGs were used to cluster tumor samples and perform survival analysis. A prognostic model was constructed based on the DEGs in CRC through regression analysis, and its predictive effect was evaluated and validated using the GEO dataset. The correlation between riskscore and tumor progression was evaluated, and Cox regression was used to verify the independence of riskscore by combining it with different clinical factors. A nomogram was drawn to predict the prognosis of CRC individuals. The differences in immune microenvironment between high-risk (H) and low-risk (L) groups were analyzed by ssGSEA and ESTIMATE. The tumor mutation burden (TMB) was calculated for the two groups. Drug sensitivity prediction was performed for the two groups. Finally, the expression levels of prognostic feature genes were validated through qPCR. Based on BM-related DEGs, CRC samples were classified into 2 clusters, with cluster 1 having significantly lower survival rates. A prognostic model was developed based on 7 genes (AGRN, TIMP1, UNC5A, SPARCL1, ADAMTS6, MMP1, and UNC5C). The model exhibited high predictive accuracy and demonstrated the potential to serve as an independent prognostic factor for predicting the prognosis of CRC individuals. A higher riskscore indicated a higher degree of tumor progression. Group H demonstrated higher levels of immune infiltration and TMB, suggesting that individuals in this group might be more suitable for immune therapy. Two first-line anti-tumor drugs, Gemcitabine and Cisplatin, with higher sensitivity to individuals in group L were obtained. The q-PCR results of the feature genes were consistent with the results of gene expression in the database. This study established a 7-gene BM-related prognostic model that could be used to analyze the immune landscape of CRC individuals and predict their sensitivity to immunotherapy and chemotherapy. This research provided a reference for the prognosis prediction and immunotherapy of CRC individuals.</p>","PeriodicalId":14891,"journal":{"name":"Journal of Applied Genetics","volume":" ","pages":"711-729"},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular and molecular changes in mucopolysaccharidosis-plus syndrome caused by a homozygous c.599G > C (p.Arg200Pro) variant of the VPS33A gene.","authors":"Zuzanna Cyske, Estera Rintz, Magdalena Narajczyk, Natalia Świątek, Lidia Gaffke, Karolina Pierzynowska, Grzegorz Węgrzyn","doi":"10.1007/s13353-025-00997-x","DOIUrl":"10.1007/s13353-025-00997-x","url":null,"abstract":"<p><p>Mucopolysaccharidosis-plus syndrome (MPSPS) is an ultrarare inherited metabolic disease (a few dozen patients diagnosed to date) which is characterised by accumulation of undegraded glycosaminoglycans (GAGs). Despite GAG storage occurs also in the groups of diseases classified as mucopolysaccharidoses (MPS), contrary to MPS, no dysfunctions of lysosomal enzymes is detected in MPSPS which is caused by mutations in the VPS33A gene. The c.1492C > T (p.Arg498Trp) variant, associated with a severe course of the disease, was found in most MPSPS patients. There are only two patients described to date with a homozygous c.599G > C (p.Arg200Pro) variant and a milder (juvenile) form. Until now, the molecular mechanism of MPSPS remained largely unknown, especially for the juvenile form. Here, a battery of cellular and molecular assays, performed using fibroblasts derived from a patient bearing the c.599G > C (p.Arg200Pro) variant of the VPS33A gene, indicated specific changes in cellular vacuoles, elevated levels of the EEA1 protein (required at the stages of the fusions of early and late endosomes, and early endosome sorting), changes in Golgi apparatus morphology, decreased levels of F-actin, and increased levels of α- and β-tubulins, as well as elevated levels of the LC3-II and p62 proteins (autophagy markers). Results of experiments presented here might suggest that severely decreased levels the p.Arg200Pro variant of VSP33A could cause defective endosomal trafficking, possibly resulting in inefficient delivery of GAGs to lysosomes, and their subsequent accumulation in cells. This might induce a cascade of secondary and tertiary disorders, finally expressing as the disease symptoms.</p>","PeriodicalId":14891,"journal":{"name":"Journal of Applied Genetics","volume":" ","pages":"683-699"},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13534158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}