Global Medical Genetics最新文献

{"title":"Molecular genetic diagnosis of autosomal dominant polycystic kidney disease - A systematic review.","authors":"Natalie Ciantar, Edith Said","doi":"10.1016/j.gmg.2026.100099","DOIUrl":"10.1016/j.gmg.2026.100099","url":null,"abstract":"<p><strong>Background: </strong>Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disorder primarily caused by pathogenic variants in <i>PKD1</i> and <i>PKD2</i>. Although molecular testing has revolutionized diagnosis, variability persists in testing strategies and diagnostic yields. This review aims to evaluate molecular genetic techniques used in ADPKD diagnosis and summarize evidence on their diagnostic performance.</p><p><strong>Method: </strong>Following a predefined protocol and PRISMA 2020 guidelines, PubMed, Scopus, and Web of Science were searched for studies published between January 2015 and August 2025. Eligible studies included ≥ 30 clinically diagnosed ADPKD participants and reported patient-level diagnostic data. Two investigators independently extracted information on testing methods, diagnostic yield, and identified genes.</p><p><strong>Results: </strong>From 23,718 records, 20 studies met inclusion criteria, with sample sizes ranging from 32 to 634 participants. Diagnostic methods included Sanger sequencing (SS), multiplex ligand-probe amplification (MLPA), long-range PCR (LR-PCR), targeted next-generation sequencing (NGS) panels, whole-exome sequencing (WES), and whole-genome sequencing (WGS). Detection rates ranged from 61% (LR-PCR) to 92% (targeted NGS). <i>PKD1</i> and <i>PKD2</i> variants accounted for 79.9% and 15.9% of cases, respectively. Additional variants were identified in <i>GANAB</i>, <i>HNF1B</i>, <i>IFT140</i>, <i>PRKCSH</i>, and <i>PKHD1</i>.</p><p><strong>Conclusion: </strong>Targeted NGS panels provided the highest diagnostic accuracy and cost-effectiveness for ADPKD. Complementary use of MLPA and LR-PCR improved detection of complex variants. Further optimization of sequencing workflows and variant interpretation will enhance diagnostic precision and clinical application. This review provides an evidence-based foundation for current diagnostic practices in ADPKD.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"13 2","pages":"100099"},"PeriodicalIF":2.1,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13050056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147623982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory role and subtype analysis of m6A modifications in dermatomyositis.","authors":"Xiang Long, Yidan Hu, Rui Tu, Youxian He","doi":"10.1016/j.gmg.2026.100097","DOIUrl":"10.1016/j.gmg.2026.100097","url":null,"abstract":"<p><strong>Background: </strong>Dermatomyositis (DM) is an uncommon autoimmune disease that presents challenges due to the lack of reliable biomarkers in clinical practice. Growing evidence suggests that N6-methyladenosine (m6A) is closely associated with the pathogenesis of autoimmune diseases.</p><p><strong>Methods: </strong>Microarray gene expression matrix for GSE46239, GSE128314, and GSE142807 were downloaded from the GEO database. Random forest (RF), support vector machine (SVM), and nomogram models were developed, with their performance subsequently compared. The identification of m6A subtypes, based on differentially expressed m6A regulatory genes, was followed by the classification of gene subtypes according to the differently expressed genes between the m6A subtypes. Both classification systems were subjected to m6A scoring analysis and visualized via a Sankey diagram.</p><p><strong>Results: </strong>We retrieved 99 dermatomyositis samples and 14 healthy samples. Using an RF model, we identified five core genes-IGFBP3, ZCCHC4, HNRNPC, WTAP, and RBM15-and constructed a predictive nomogram model. Two m6A clusters were developed. Cluster A exhibited a significant increase of CD56-bright natural killer cells, immature B cells, plasmacytoid dendritic cells, regulatory T cells, and type 1 T helper cells distinct from cluster B (p < 0.05). Based on 32 significantly distinctly expressed genes between m6A subtypes (p < 0.05), we further reproduced two m6A gene subtypes. The Sankey diagram showed significant concordance among m6A scores, m6A subtypes, and m6A gene subtypes.</p><p><strong>Conclusion: </strong>m6A regulatory genes significantly influence the pathogenesis of dermatomyositis. In this work, we built a predictive nomogram model, comprehensively evaluated two classification methods, and provided new insights for patient classification.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"13 1","pages":"100097"},"PeriodicalIF":2.1,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13015724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147522424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Can automated copy number variation pathogenicity prediction tools replace manual review under the ACMG framework? A clinical validation.","authors":"Yingying Zhang, Xiuming Zhang, Dayang Chen","doi":"10.1016/j.gmg.2026.100096","DOIUrl":"10.1016/j.gmg.2026.100096","url":null,"abstract":"<p><strong>Background: </strong>Copy Number Variation (CNV) is associated with numerous complex diseases, yet their pathogenicity assessment remains heavily dependent on manual expert review, a process that is cumbersome and time-consuming. Although a variety of automated tools for CNV pathogenicity prediction have been developed, systematic assessments of their performance and clinical generalizability under the five-category classification framework defined by ACMG standards remain scarce.</p><p><strong>Methods: </strong>This study constructed an expert-reviewed CNV benchmark dataset. Under the ACMG five-category system, it systematically compared the classification prediction capabilities of five prediction tools across both deletion and duplication CNV samples. Furthermore, it assessed their applicability in real clinical samples and evaluated potential biases towards specific variations.</p><p><strong>Results: </strong>The study indicates that different tools exhibit performance variations and specialised strengths across different classification tasks, yet overall capability in distinguishing clinical risk boundaries across the five categories remains inadequate. Among these, AnnotSV demonstrated outstanding performance in predicting pathogenic samples, achieving accuracy rates of 95.16% and 86.39% on the deletion and duplication benchmark datasets respectively. ClassifyCNV demonstrated optimal performance in variant of uncertain significance classification with an accuracy of 95.33%. Furthermore, all models exhibited significantly superior five-category discrimination capabilities for deletion samples compared with duplication samples, revealing pronounced performance biases across variant types.</p><p><strong>Conclusion: </strong>Current automated CNV prediction tools demonstrate higher discriminatory capacity for deletion variants than for duplications; however, they remain insufficient to fully replace manual expert review within the ACMG five-category framework. Further optimisation using multicentre, consistently curated clinical gold-standard datasets is required to improve their reliability and clinical applicability.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"13 2","pages":"100096"},"PeriodicalIF":2.1,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13018948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147575673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pediatric toe-walking cohort with heterozygous SBF1 variants: A phenotypic description.","authors":"David Pomarino, Amel Sidi Athmane, Bastian Fregien, Alexander Nazarkin, Kevin M Rostásy","doi":"10.1016/j.gmg.2026.100095","DOIUrl":"10.1016/j.gmg.2026.100095","url":null,"abstract":"<p><strong>Purpose: </strong>Persistent toe walking is frequently labeled idiopathic; however, targeted genetic testing in selected cohorts can identify variants in genes implicated in neuromuscular disease. SBF1 is a known cause of autosomal recessive Charcot-Marie-Tooth disease type 4B3 (CMT4B3), whereas the clinical relevance of heterozygous SBF1 variants-particularly variants of uncertain significance (VUS)-remains unclear. We aimed to describe, in an exploratory manner, the clinical features of children with persistent toe walking in whom heterozygous SBF1 variants were identified, and to contextualize these observations using published CMT4B3 families and Human Phenotype Ontology (HPO) feature frequencies.</p><p><strong>Methods: </strong>We retrospectively analyzed children referred to a specialized toe-walking clinic who underwent a standardized blinded clinical assessment and targeted 49-gene next-generation sequencing. Individuals with alternative sequencing approaches or known non-genetic causes of toe walking were excluded. Heterozygous SBF1 variants were summarized using HGVS nomenclature, ACMG classification, population allele frequency, and report date. Phenotypic frequencies were compared with published SBF1-related CMT4B3 families and with HPO-reported feature frequencies for CMT4B3.</p><p><strong>Results: </strong>The cohort comprised 86 children (mean age 9.5 years), all with persistent toe walking. Common findings included skeletal features (e.g., pes cavus and lumbar hyperlordosis), whereas muscle weakness and deep tendon reflex abnormalities were less frequent than reported in recessive CMT4B3 families. Genetic testing identified a spectrum of <b>heterozygous SBF1 variants</b>, predominantly classified as <b>VUS</b>.</p><p><strong>Conclusions: </strong>In this referral-based cohort, heterozygous SBF1 variants were observed in children with persistent toe walking and accompanying mild neuromotor/musculoskeletal features that partially overlap with reported CMT4B3 phenotypes; however, these findings are descriptive and do not establish causality or enrichment. Longitudinal follow-up, segregation/phase determination, and electrophysiological studies are needed to clarify clinical significance, potential biallelic configurations in some individuals, and possible gene-dosage or modifier effects.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"13 1","pages":"100095"},"PeriodicalIF":2.1,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12926636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147285439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel <i>PRKACB</i> variant associated with bilateral postaxial polydactyly and intrauterine growth restriction: A case report and literature review.","authors":"Yan Zhang, Wenlong Shen, Yaer Lv, Jue Zhao, Junjie Wu, Yang Wang, Xujun He, Xiaohua Tang","doi":"10.1016/j.gmg.2025.100085","DOIUrl":"10.1016/j.gmg.2025.100085","url":null,"abstract":"<p><strong>Objective: </strong>To characterize the clinical features of a fetus with postaxial polydactyly caused by a <i>de novo PRKACB</i> gene variant and to perform a genetic analysis.</p><p><strong>Methods: </strong>A pregnant woman who presented to Zhejiang Provincial People's Hospital on 4 December 2024 was enrolled in this study. Fetal clinical data were collected, and genomic DNA was extracted from the fetus and both parents. Clinical whole-exome sequencing (WES) was performed on the trio (fetus and both parents). Candidate variants were identified and validated by Sanger sequencing, followed by bioinformatics analysis. This study was approved by the Medical Ethics Committee of Zhejiang Provincial People's Hospital (approval number: QT2025076).</p><p><strong>Results: </strong>Prenatal ultrasonography revealed bilateral postaxial polydactyly and several fetal biometric measurements that were inconsistent with gestational age. The clinical diagnoses were intrauterine growth restriction and polydactyly. WES identified a <i>de novo</i> heterozygous variant (c.802 G>A; p.Asp268Asn) in exon 8 of the fetal <i>PRKACB</i> gene (NM_182948.4). According to the ACMG variant-classification guidelines, this variant was interpreted as likely pathogenic (PS2_Moderate, PM1, PM2_Supporting and PP3). AlphaFold-based structural prediction indicated that the PRKACB p.Asp268Asn substitution resulted in the loss of two hydrogen bonds, thereby altering the protein's three-dimensional conformation and affecting structural stability.</p><p><strong>Conclusion: </strong>The <i>PRKACB</i> gene c.802 G>A (p.Asp268Asn) variant is a potential genetic cause of bilateral postaxial polydactyly in the fetus. Identification of this variant expands the known mutational spectrum of <i>PRKACB</i> gene and provides an important reference for genetic counselling and prenatal diagnosis.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"12 4","pages":"100085"},"PeriodicalIF":1.5,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12756693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic susceptibility of <i>IKZF1</i>, <i>ARID5B</i>, and <i>CEBPE</i> polymorphisms to childhood acute lymphoblastic leukemia in Chinese populations: a case-control study.","authors":"Xiaoqing Cao, Yong Wang, Yurou Kang, Muhammad Usman Abubakar, Yanli Yang, Daihua Fang, Bangshun He","doi":"10.1016/j.gmg.2025.100084","DOIUrl":"10.1016/j.gmg.2025.100084","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to evaluate the association of single nucleotide polymorphisms (SNPs) in <i>IKZF1</i>, <i>ARID5B</i>, and <i>CEBPE</i> with acute lymphoblastic leukemia (ALL) susceptibility in Chinese children.</p><p><strong>Methods: </strong>A case-control study was conducted involving 360 ALL patients and 398 healthy controls. Nine SNPs were genotyped, and their associations with ALL risk were analyzed using logistic regression under various genetic models. Multifactor dimensionality reduction (MDR) analysis was employed to investigate SNP-SNP interactions.</p><p><strong>Results: </strong>Seven of the nine SNPs were significantly associated with ALL susceptibility. Specifically, <i>IKZF1</i> SNPs (rs11980379, rs4132601, rs10272724) and a <i>CEBPE</i> SNP (rs4982731) were associated with an increased risk of ALL. In contrast, <i>ARID5B</i> SNPs (rs10994982, rs10821938) and another <i>CEBPE</i> SNP (rs2144827) were associated with a reduced risk. Stratified analyses revealed age- and sex-specific associations. MDR analysis identified significant SNP-SNP interactions, with a robust four-SNP model (rs10994982, rs2144827, rs10272724, rs10821938) showing the best predictive performance for ALL risk.</p><p><strong>Conclusion: </strong>Specific SNPs in <i>IKZF1</i>, <i>ARID5B</i>, <i>CEBPE</i> and their interactions are associated with childhood ALL susceptibility in Chinese populations, providing references for ALL risk stratification.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"12 4","pages":"100084"},"PeriodicalIF":1.5,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12755977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistent toe walking as a prominent feature in pediatric PMP22- Related neuropathies: A retrospective cohort study.","authors":"David Pomarino, Kevin M Rostásy, Bastian Fregien, Jan Oliver Schönfeldt, Alexander Nazarkin","doi":"10.1016/j.gmg.2025.100082","DOIUrl":"10.1016/j.gmg.2025.100082","url":null,"abstract":"<p><strong>Purpose: </strong>Persistent toe walking in children is often considered idiopathic; however, increasing evidence suggests that alterations in the PMP22 gene-implicated in Charcot-Marie-Tooth disease type 1 A (CMT1A) and Hereditary Neuropathy with Liability to Pressure Palsies (HNPP)-may contribute to its pathogenesis. This study investigates the association between PMP22 variants (duplications, deletions, and point mutations) and toe walking in children, aiming to delineate their clinical and genetic characteristics.</p><p><strong>Methods: </strong>A retrospective analysis was performed on 22 pediatric patients (mean age: 7.7 years) with persistent toe walking and confirmed PMP22 variants identified through a 49-gene next-generation sequencing (NGS) panel. In selected cases, Multiplex Ligation-dependent Probe Amplification (MLPA) was applied to confirm copy number variations. Comprehensive clinical evaluations included musculoskeletal, neurological, and developmental assessments.</p><p><strong>Results: </strong>All identified variants demonstrated dominant inheritance. Pathogenic variants were present in 54.5 % of patients, likely pathogenic in 31.8 %, and variants of uncertain significance (VUS) in 13.6 %. Among pathogenic cases, most carried PMP22 duplications, one had a deletion, and the remainder harbored the missense variant p.(Thr118Met). The three VUS carriers exhibited comparatively milder phenotypes, such as muscle cramps, lumbar hyperlordosis, mild dorsiflexion restriction, hyporeflexia, pes cavus, and clinodactyly/brachydactyly; only one presented with tremor. Lumbar hyperlordosis (90.9 %) and pes cavus (90.9 %) were the most consistent findings.</p><p><strong>Conclusions: </strong>Persistent toe walking may represent an early sign of PMP22-related neuropathies rather than a benign idiopathic gait pattern. The predominance of PMP22 duplications and characteristic neuromuscular features highlight the clinical utility of integrating NGS and MLPA testing for accurate diagnosis, targeted management, and genetic counseling.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"12 4","pages":"100082"},"PeriodicalIF":1.5,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12744280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145858420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global comprehensive transcriptomic and proteomic analyses of murine terminal erythroid differentiation.","authors":"Xiao-Yue Tang, Jia-Huan Chen, Ran Yang, Hong Fan, Ke Yang, Tao Ding, Qiao-Chu Wang, Ye-Hong Yang, Yue Wu, Zhi-Yi Zhang, Chun-Mei Shi, Xue-Hui Liu, Jiang-Feng Liu, Xiang Lv, Jun-Tao Yang","doi":"10.1016/j.gmg.2025.100083","DOIUrl":"10.1016/j.gmg.2025.100083","url":null,"abstract":"<p><strong>Background: </strong>Terminal erythroid differentiation (TED) is the maturation process of proerythroblasts into enucleated erythrocytes. Animal models are essential for studying red blood cell disorders.</p><p><strong>Methods: </strong>We isolated erythroblasts at different TED stages from mouse bone marrow using FACS and performed integrated multi-omics analyses.</p><p><strong>Results: </strong>We developed a stage-specific transcriptome and proteome profile, enhancing murine TED databases. The most significant changes occurred during the transition from proerythroblasts to basophilic erythroblasts, characterized by immune function suppression and activation of erythroid processes. Global gene and protein expression dynamics showed that orthochromatic erythroblasts exit the cell cycle, with transcription cofactors histone deacetylase 1(HDAC1), histone deacetylase 2(HDAC2), and cell division control protein 6 homolog (CDC6), playing key roles in cell cycle regulation. Additionally, autophagy was initiated at the basophilic stage, indicated by increased autophagy-related gene (ATG) mRNA levels and activation of autophagy marker proteins like microtubule associated protein 1 light chain 3 beta (LC3-I), optineurin (OPTN), and ATGs, including Atg7, Atg4b, Atg3, and Atg2b.</p><p><strong>Conclusions: </strong>Overall, we have generated a foundational murine transcriptome and proteome dataset, providing insights into the functional dynamics and regulatory mechanisms of terminal erythroid differentiation.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"12 4","pages":"100083"},"PeriodicalIF":2.1,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12744273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145858355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of IL-6 and IL-1β Gene coding and study on specific clearance using histidine-grafted PVDF membranes.","authors":"Ke Li, JuanJuan Liu, Kuo Zhang, Hui Liu, Yi Yang, Ren Na, Hui Ma, XiaoJian Cui","doi":"10.1016/j.gmg.2025.100080","DOIUrl":"10.1016/j.gmg.2025.100080","url":null,"abstract":"<p><p>Severely infected patients produce large amounts of inflammatory cytokines, such as interleukin-6 (IL-6) and interleukin-1β (IL-1β), leading to a \"cytokine storm\", which is a clinically refractory condition. Because IL-6 and IL-1β differ significantly in gene family, chromosomal location, protein structure, and signaling pathways, existing techniques are ineffective at simultaneously removing cytokines. This work developed a novel blood purification material by chemically grafting histidine onto a polyvinylidene fluoride (PVDF) membrane. ATR-FTIR and XPS analyses confirmed the successful grafting of histidine onto the PVDF membrane. Following histidine grafting, the membrane's adsorption capacity for IL-6 in aqueous solution increased with histidine concentration. The optimized histidine-grafted PVDF membrane achieved adsorption rates of (36 ± 4)% for IL-6 and (63 ± 5) % for IL-1β in plasma. Additionally, the histidine-grafted PVDF membrane demonstrated enhanced biocompatibility, exhibiting a low hemolysis rate, minimal adsorption of red blood cells and platelets, and anticoagulant properties without activating the coagulation cascade. This histidine-grafted PVDF membrane offers a promising new therapeutic strategy for treating severe infections and holds significant potential for clinical application.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"12 4","pages":"100080"},"PeriodicalIF":1.5,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12670094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145670201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinformatics differential expression analysis of the effect of cannabidiol in chronic myeloid leukaemia cell line.","authors":"Petar P Donchev, Svetla T Danova","doi":"10.1016/j.gmg.2025.100076","DOIUrl":"10.1016/j.gmg.2025.100076","url":null,"abstract":"<p><p>Chronic myeloid leukaemia (CML) is the first clonal myeloproliferative disorder of pluripotent stem cells to be associated with a specific genetic abnormality, the Philadelphia chromosome, bearing the <i>BCR-ABL1</i> fusion oncogene. Tyrosine kinase inhibitors are used as first-line treatment for the chronic phase of CML, although alternative treatments are necessary for resistant cases. Cannabidiol (CBD) is a major constituent of hemp oil that exerts a broad range of pharmacological effects in various malignancies. However, its molecular mechanisms in leukaemia remain unclear. In the present study, Imatinib-sensitive K-562S cells were subjected to CBD treatment (IC50: 17.69 μM) for 4 and 12 h, followed by RNA sequencing to identify differentially expressed genes (DEGs). The subsequent transcriptomic profiling revealed 3518 DEGs at 12 h and 3433 DEGs at 4 h of treatment, including significant modulation of metallothionein-regulated oxidative stress responses (<i>MT1</i>, <i>MT2</i>, and <i>SLC30A2</i>) and p53-mediated apoptosis (<i>TP53TG3</i>, <i>DDIT4</i>, <i>BBC3</i>, <i>CHAC1</i>, <i>NOXA1</i>, and <i>DAPK2</i>). Additionally, the DEGs were enriched in alterations in immune signalling pathways-including type I interferon activation and PI3K-Akt-mTOR and Toll-like receptor signalling-crucial in leukaemia progression, as well as variations in lipid metabolism and mitochondrial homeostasis. The results presented in this study validate the considerable potential of CBD to induce broad transcriptional and signalling alterations, related to immune modulation, apoptosis, and metabolic processes in K-562S cells. These findings provide novel insights into the therapeutic potential of CBD and lay the groundwork for further investigation into its precision applications in haematological malignancies.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"12 4","pages":"100076"},"PeriodicalIF":2.1,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12508839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}