Genes最新文献

{"title":"Research on SSR Genetic Molecular Markers and Morphological Differences of Different <i>Pelodiscus sinensis</i> Populations.","authors":"Yixin Liang, Changqing Huang, Pei Wang, Hewei Xiao, Zi'ao Wang, Jiawei Zeng, Xiaoqing Wang, Shuting Xiong, Yazhou Hu, Qin Qin","doi":"10.3390/genes16030318","DOIUrl":"10.3390/genes16030318","url":null,"abstract":"<p><strong>Background/objectives: </strong>The Chinese soft-shelled turtle (<i>Pelodiscus sinensis</i>) is an important species in freshwater aquaculture. Genetic admixture and degradation due to rapid industry expansion threaten sustainable development. This study aims to assess the genetic diversity and structure of six <i>P. sinensis</i> populations for better management.</p><p><strong>Methods: </strong>We combined morphological analysis and microsatellite markers to evaluate the genetic diversity of six populations. A discriminant function based on morphology was developed, achieving 71.4% classification accuracy. Two SSR markers were identified to specifically distinguish the HS population.</p><p><strong>Results: </strong>The six populations were classified into three subgroups. Frequent gene flow was observed among the CY, W, and DT populations, with most genetic variation occurring within individuals. However, significant genetic differentiation was detected between populations. While gene flow enhanced diversity, it suppressed differentiation.</p><p><strong>Conclusions: </strong>This study provides insights into the genetic structure and diversity of six <i>P. sinensis</i> populations. The discriminant function and SSR markers offer a basis for germplasm conservation and management, supporting sustainable aquaculture development.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729724","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":"The Mitochondrial Genome of the Springtail <i>Semicerura bryophila</i> (Collembola): New Data Call into Question the Relevance of the Subfamilies of the Isotomidae.","authors":"Zhijng Xie, Mingxin Zheng, Yueying Li, Shiyu Du, Ruslan Saifutdinov, Mikhail Potapov, Xin Sun, Donghui Wu","doi":"10.3390/genes16030315","DOIUrl":"10.3390/genes16030315","url":null,"abstract":"<p><p><b>Background</b>: <i>Semicerura bryophila</i> Potapov & Sun, 2020 is a soil-dwelling springtail belonging to the family Isotomidae. The phylogenetic relationships among species of this group remain controversial due to a lack of molecular data. Therefore, in this study, we sequenced the mitochondrial genome of <i>S. bryophila</i>, analyzed the characterization of the mitochondrial genome, and investigated the phylogenetic relationships of Isotomidae. <b>Methods</b>: The mitochondrial genome of <i>S. bryophila</i> was sequenced and assembled. We analyzed the sequence length, nucleotide composition, and evolutionary relationships within the Isotomidae family, incorporating data from twelve previously published mitochondrial genomes. <b>Results</b>: The length of the <i>S. bryophila</i> mitogenome is 15,247 bp and comprises 13 protein-coding genes, 22 tRNAs, and two <i>rRNA</i>s, arranged in a typical order. Its base composition is as follows: A = 38.05%, T = 33.64%, G = 10.17%, and C = 15.03%. Phylogenetic analysis based on the mitogenome revealed that the monophyly of Isotomidae and the paraphyletic grouping of <i>Semicerura</i> and <i>Folsomotoma</i>, supporting their closer relationship with the subfamily Anurophorinae rather than to Isotominae. The analysis validated subfamily Anurophorinae, identified Pachyotominae as a part of Anurophorinae, and suggested that Isotominae is paraphyletic. <b>Conclusions</b>: The present study provides valuable mitochondrial information for the classification of <i>S. bryophila</i> and offers new insights into the taxonomic and evolutionary studies within the genus <i>Semicerura</i>.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728490","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":"Roles of miR-223 in Platelet Function and High On-Treatment Platelet Reactivity: A Brief Report and Review.","authors":"Shayan Askari, Lawrence E Goldfinger","doi":"10.3390/genes16030312","DOIUrl":"10.3390/genes16030312","url":null,"abstract":"<p><strong>Background: </strong>Platelets are highly enriched in microRNAs (miRNAs), which are genomically encoded 19-25 nucleotide non-coding RNAs that target complementary mRNAs through total or near-total base pairing. MiR-223 is among the most abundant miRNAs in human and murine platelets, but despite ongoing investigations in recent years, miR-223 roles in platelet physiology and its putative roles in high on-treatment platelet reactivity (HTPR) remain controversial, as studies showed varying findings.</p><p><strong>Objectives: </strong>In the current hybrid review/report, we aim to compare studies that investigated miR-223 in platelet function and HTPR. Additionally, we briefly report our own findings on murine miR-223-deficient platelets.</p><p><strong>Methods: </strong>We have thoroughly searched the literature and found three studies that investigated the roles of miR-223 in platelet function by utilizing miR-223 global knockout mice, and three studies that explored the association between miR-223 and residual platelet reactivity by measuring miR-223 levels in platelets of patients treated with clopidogrel for cardiac artery disease. We assessed platelet function in response to different agonists and evaluated P2y12 levels in male and female miR-223-deficient platelets.</p><p><strong>Results: </strong>Integrin activation and α granule secretion were similar between WT and KO platelets in response to all agonists in platelets from both female and male mice, although both genotypes showed elevated thrombin response in females compared to males.</p><p><strong>Conclusions: </strong>In all studies, including ours, taken together, miR-233 appears to play a modest role in platelet function and development of HTPR.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729725","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":"LncRNAs Ride the Storm of Epigenetic Marks.","authors":"Giulia Gaggi, Clinton Hausman, Soomin Cho, Brianna C Badalamenti, Bon Q Trinh, Annalisa Di Ruscio, Simone Ummarino","doi":"10.3390/genes16030313","DOIUrl":"10.3390/genes16030313","url":null,"abstract":"<p><p>Advancements in genome sequencing technologies have uncovered the multifaceted roles of long non-coding RNAs (lncRNAs) in human cells. Recent discoveries have identified lncRNAs as major players in gene regulatory pathways, highlighting their pivotal role in human cell growth and development. Their dysregulation is implicated in the onset of genetic disorders and age-related diseases, including cancer. Specifically, they have been found to orchestrate molecular mechanisms impacting epigenetics, including DNA methylation and hydroxymethylation, histone modifications, and chromatin remodeling, thereby significantly influencing gene expression. This review provides an overview of the current knowledge on lncRNA-mediated epigenetic regulation of gene expression, emphasizing the biomedical implications of lncRNAs in the development of different types of cancers and genetic diseases.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729638","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":"Pharmacogenetic Factors Shaping Treatment Outcomes in Chronic Obstructive Pulmonary Disease.","authors":"Charikleia Ntenti, Thomas Nikos Misirlis, Antonis Goulas","doi":"10.3390/genes16030314","DOIUrl":"10.3390/genes16030314","url":null,"abstract":"<p><p>Chronic Obstructive Pulmonary Disease (COPD) manifests as a genetically diverse and intricate lung condition with various subtypes. The development of the disease and response to treatment are influenced by the interplay between genetic and environmental factors. The predominant therapeutic approaches include bronchodilator therapy and corticosteroid treatment. Studies in COPD pharmacogenetics involve genome-wide association (GWA) studies, gene profiling, whole-genome sequencing, and other omics-based investigations. Many of these investigations have focused on the association between genetic variations and the response to β2 agonist treatment. Additionally, several studies have explored the impact of gene variations on the response to inhaled corticosteroid (ICS) treatment, with a specific focus on polymorphisms in the glucocorticoid receptor (GR) signaling pathway. However, a significant challenge lies in the inconclusive or inconsistent results of these pharmacogenetic studies, underscoring the research community's struggle to provide sufficient evidence for the clinical implementation of COPD pharmacogenetics. To address these challenges, further research and larger genome-wide studies are essential. These efforts aim to uncover additional COPD subtypes, identify predictors of treatment response, and discover novel genetic markers for COPD. The integration of genomics, detailed evaluations such as chest CT scans, spirometry tests, and blood analyses, along with DNA collection in clinical research, is critical for translating COPD pharmacogenetics into clinical practice. Furthermore, advancing our understanding of the complex interactions between genetics, phenotypes, and environmental factors will be pivotal for improving individualized prognostic assessments and enhancing treatment outcomes in COPD.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729707","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":"Identification of a Homozygous Variant in the <i>CYP21A2</i> Gene by Next-Generation Sequencing Analysis of Circulating Cell-Free Fetal DNA.","authors":"Nadia Petrillo, Simone Marcella, Roberto Sirica, Monica Ianniello, Raffaella Ruggiero, Alessio Mori, Rosa Castiello, Cristina Ramiro, Rossana D'Angelo, Giuliano Pennacchio, Ermanno Barletta, Roberto Passaro, Antonio Fico, Giovanni Savarese","doi":"10.3390/genes16030311","DOIUrl":"10.3390/genes16030311","url":null,"abstract":"<p><strong>Background/objectives: </strong>Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder caused by mutations in the <i>CYP21A2</i> gene associated with 21-hydroxylase deficiency and increased levels of adrenal androgens. Affected females are at risk of ambiguous genitalia, while affected males show sexual precocity. Here, we present a case of a newborn female patient, characterized by ambiguous genitalia and previously identified as low risk for common aneuploidies by non-invasive prenatal testing (NIPT).</p><p><strong>Methods: </strong>We performed a NIPT, which showed a 46, XX genotype, confirmed by karyotype on the newborn's DNA extracted lymphocytes. For clinical suspicion of CAH, we performed reverse dot blot and Multiple Ligation-dependent Probe Amplification (MLPA) of the <i>CYP21A2</i> gene on the patients and her parents' DNA. Then, we performed on mother's plasma NGS analysis with an in-house developed panel of genes for monogenic diseases, including the <i>CYP21A2</i> gene.</p><p><strong>Results: </strong>Reverse dot blot and MLPA detected the presence of the c.290-13A/C>G (I2 splice) mutation in heterozygosity in the parents and in homozygosity in the child, respectively. NGS detected the c.290-13A/C>G (I2splice) mutation in cell-free fetal DNA (cfDNA) in mother's plasma with a variant allele frequency (VAF) of 67% with a fetal fraction (FF) of 5%. This latter suggests the presence of the variant both in the mother and in newborn cfDNA.</p><p><strong>Conclusions: </strong>The study reinforces the hypothesis that cfDNA can be used to identify point mutations, small insertions and/or deletions for the diagnosis of monogenic diseases, reducing the number of invasive tests and the risk of early miscarriages. Early detection of mutations in genes causing sexual development disorders could make it possible to start therapy in the womb.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729700","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":"Cell Cycle-Based Molecular Features via Synthetic Lethality and Non-Coding RNA Interactions in Cancer.","authors":"Shizheng Xiong, Jiaming Jin, Xinmiao Zhao, Yang Zhao, Zhiheng He, Haochuan Guo, Chengjun Gong, Jiafeng Yu, Li Guo, Tingming Liang","doi":"10.3390/genes16030310","DOIUrl":"10.3390/genes16030310","url":null,"abstract":"<p><strong>Background: </strong>The cell cycle, a critical and intricate biological process, comprises various phases, and its dysregulation plays a pivotal role in tumorigenesis and metastasis. The exploration of cell cycle-based molecular subtypes across pan-cancers, along with the application of synthetic lethality concepts, holds promise for advancing cancer therapies.</p><p><strong>Methods: </strong>A pan-cancer analysis was conducted to assess the cell cycle serves as a reliable signature for classifying molecular subtypes and to understand the potential clinical application of genes as potential drug targets based on synthetic lethality.</p><p><strong>Results: </strong>Molecular subtypes derived from cell cycle features in certain cancers, particularly kidney-related malignancies, exhibited distinct immune characteristics. Synthetic lethal interactions within the cell cycle pathway were common, with significant genetic interactions further identifying potential drug targets through the exploitation of genetic relationships with key driver genes. Additionally, miRNAs and lncRNAs may influence the cell cycle through miRNA:mRNA interactions and ceRNA networks, thereby enriching the genetic interaction landscape.</p><p><strong>Conclusions: </strong>These findings suggest that the cell cycle pathway could serve as a promising molecular subtype signature to enhance cancer prognostication and offer potential targets for anticancer drug development through synthetic lethality.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729648","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":"Integrative In Silico Analysis to Identify Functional and Structural Impacts of nsSNPs on Programmed Cell Death Protein 1 (PD-1) Protein and UTRs: Potential Biomarkers for Cancer Susceptibility.","authors":"Hakeemah Al-Nakhle, Retaj Al-Shahrani, Jawanah Al-Ahmadi, Wesal Al-Madani, Rufayda Al-Juhani","doi":"10.3390/genes16030307","DOIUrl":"10.3390/genes16030307","url":null,"abstract":"<p><p><b>Background:</b> Programmed cell death protein 1 (PD-1), encoded by the <i>PDCD1</i> gene, is critical in immune checkpoint regulation and cancer immune evasion. Variants in <i>PDCD1</i> may alter its function, impacting cancer susceptibility and disease progression. <b>Objectives:</b> This study evaluates the structural, functional, and regulatory impacts of non-synonymous single-nucleotide polymorphisms (nsSNPs) in the <i>PDCD1</i> gene, focusing on their pathogenic and oncogenic roles. <b>Methods:</b> Computational tools, including PredictSNP1.0, I-Mutant2.0, MUpro, HOPE, MutPred2, Cscape, Cscape-Somatic, GEPIA2, cBioPortal, and STRING, were used to analyze 695 nsSNPs in the PD1 protein. The analysis covered structural impacts, stability changes, regulatory effects, and oncogenic potential, focusing on conserved domains and protein-ligand interactions. <b>Results:</b> The analysis identified 84 deleterious variants, with 45 mapped to conserved regions like the Ig V-set domain essential for ligand-binding interactions. Stability analyses identified 78 destabilizing variants with significant protein instability (ΔΔG values). Ten nsSNPs were identified as potential cancer drivers. Expression profiling showed differential <i>PDCD1</i> expression in tumor versus normal tissues, correlating with improved survival in skin melanoma but limited value in ovarian cancer. Regulatory SNPs disrupted miRNA-binding sites and transcriptional regulation, affecting <i>PDCD1</i> expression. STRING analysis revealed key PD-1 protein partners within immune pathways, including PD-L1 and PD-L2. <b>Conclusions:</b> This study highlights the significance of <i>PDCD1</i> nsSNPs as potential biomarkers for cancer susceptibility, advancing the understanding of PD-1 regulation. Experimental validation and multi-omics integration are crucial to refine these findings and enhance theraputic strategies.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728740","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":"Genome-Wide Identification and Expression Analysis of CrRLK1-like Gene Family in Potatoes (<i>Solanum tuberosum</i> L.) and Its Role in PAMP-Triggered Immunity.","authors":"Yazhou Bao, Ru Zhao, Sixian Hu, Xiaoli Li, Like Wang, Ji Wang, Junbin Ji, Weiduo Wang, Changqing Zhu, Jiajia Chen, Ailing Ben, Jinfeng Peng, Tingli Liu","doi":"10.3390/genes16030308","DOIUrl":"10.3390/genes16030308","url":null,"abstract":"<p><strong>Background: </strong>The <i>Catharanthus roseus</i> receptor-like kinase 1-like (CrRLK1L) subfamily, a specialized group within receptor-like kinases (RLKs), was initially identified in <i>C. roseus</i> cell cultures. CrRLK1L plays an important role in the growth, development and stress response of plants. Although CrRLK1L genes have been characterized across multiple plant species, their biological and genetic functions in potatoes (<i>Solanum tuberosum</i>) remains poorly elucidated.</p><p><strong>Methods: </strong>a genome-wide investigation, phylogenetic analysis, chromosome localization, exon-intron structure, conserved motifs, stress-responsive <i>cis</i>-elements, tissue-specific expression patterns, and their effects on pathogen associated molecular patterns (PAMPs) induced reactive oxygen species (ROS) production were analyzed.</p><p><strong>Results: </strong>A total of 29 CrRLK1L genes were identified in the <i>S. tuberosum</i> genome, unevenly distributed across 10 chromosomes and divided into three groups. Tissue-specific expression analysis revealed seven genes highly expressed in all tissues, while CrRLK1L13 was specific to stamens and flowers. Under stress conditions (mannitol, salt, hormone, and heat), StCrRLK1L genes exhibited diverse expression patterns. Functional characterization in <i>Nicotiana benthamiana</i> identified seven ROS suppressors and four ROS enhancers, implicating their roles in PAMP-triggered immunity.</p><p><strong>Conclusions: </strong>This study provides valuable insights into the StCrRLK1L gene family, enhancing our understanding of its functions, particularly in plant innate immunity.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729690","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":"Phenotypical Characterization of C9ALS Patients from the Emilia Romagna Registry of ALS: A Retrospective Case-Control Study.","authors":"Andrea Ghezzi, Giulia Gianferrari, Elisa Baldassarri, Elisabetta Zucchi, Ilaria Martinelli, Veria Vacchiano, Luigi Bonan, Lucia Zinno, Andi Nuredini, Elena Canali, Matteo Gizzi, Emilio Terlizzi, Doriana Medici, Elisabetta Sette, Marco Currò Dossi, Simonetta Morresi, Mario Santangelo, Alberto Patuelli, Marco Longoni, Patrizia De Massis, Salvatore Ferro, Nicola Fini, Cecilia Simonini, Serena Carra, Giovanna Zamboni, Jessica Mandrioli","doi":"10.3390/genes16030309","DOIUrl":"10.3390/genes16030309","url":null,"abstract":"<p><strong>Background/objectives: </strong><i>C9ORF72</i> expansion is associated with significant phenotypic heterogeneity. This study aimed to characterize the clinical features of C9ALS patients from the Emilia Romagna ALS registry (ERRALS) and compare them with non-mutated ALS (nmALS) patients matched for sex, age at onset, and diagnostic delay, sourced from the same register.</p><p><strong>Methods: </strong>In total, 67 C9ALS patients were compared to 201 nmALS. Clinical data, phenotype, and prognostic factors were analyzed in the two groups and within the C9ALS group after stratification by sex.</p><p><strong>Results: </strong>C9ALS patients displayed a higher disease progression rate and shorter times to gastrostomy and invasive ventilation, despite no differences in overall survival. Female C9ALS had a more severe bulbar and upper motor neuron involvement compared to males. Cognitive and behavioral symptoms were more common in the C9ALS group, and the former was an independent prognostic factor. Prevalences of, autoimmune diseases, and dyslipidemia were significantly higher among C9ALS patients.</p><p><strong>Conclusions: </strong>In our dataset, we show an overall increased disease progression rate in C9ALS patients and hint at sex-specific discrepancies in some phenotypical characteristics. We also suggest a possible clinically relevant involvement of <i>C9ORF72</i> expansion in metabolism and autoimmunity.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729708","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}