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Abstract: Epigenetic dysregulation has emerged as an important etiological mechanism of neurodevelopmental disorders (NDDs). Pathogenic variation in epigenetic regulators can impair deposition of histone post-translational modifications leading to aberrant spatiotemporal gene expression during neurodevelopment. The male-specific lethal (MSL) complex is a prominent multi-subunit epigenetic regulator of gene expression and is responsible for histone 4 lysine 16 acetylation (H4K16ac). Using exome sequencing, here we identify a cohort of 25 individuals with heterozygous de novo variants in MSL complex member MSL2. MSL2 variants were associated with NDD phenotypes including global developmental delay, intellectual disability, hypotonia, and motor issues such as coordination problems, feeding difficulties, and gait disturbance. Dysmorphisms and behavioral and/or psychiatric conditions, including autism spectrum disorder, and to a lesser extent, seizures, connective tissue disease signs, sleep disturbance, vision problems, and other organ anomalies, were observed in affected individuals. As a molecular biomarker, a sensitive and specific DNA methylation episignature has been established. Induced pluripotent stem cells (iPSCs) derived from three members of our cohort exhibited reduced MSL2 levels. Remarkably, while NDD-associated variants in two other members of the MSL complex (MOF and MSL3) result in reduced H4K16ac, global H4K16ac levels are unchanged in iPSCs with MSL2 variants. Regardless, MSL2 variants altered the expression of MSL2 targets in iPSCs and upon their differentiation to early germ layers. Our study defines an MSL2-related disorder as an NDD with distinguishable clinical features, a specific blood DNA episignature, and a distinct, MSL2-specific molecular etiology compared to other MSL complex-related disorders
Keywords: MSL2, male-specific lethal complex, neurodevelopmental syndrome, epigenetics, autism, epilepsy, connective tissue, episignature, iPSC
Published in DiRROS: 03.06.2026; Views: 230; Downloads: 229
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Abstract: Background Both suicidal and non-suicidal self-injuring behaviors (NSSI) are common during adolescence In Slovenia, adolescent suicide rates are high, making suicide the leading cause of death in the year 2022 in this age group. These behaviors are influenced by a complex interplay of environmental, psychological, and genetic factors. Previous research has identified risk and protective factors mainly for suicidal behavior in adults, a notable gap in understanding these factors in adolescents remains, especially for NSSI. Notably there is an important lack of effective clinical tools or psychometric assessment methods to reliably assess the risk for either suicidal or NSSI behaviors in acutely hospitalized adolescents. Methods and analysis The proposed study uses a mixed-method observational design consisting of a prospective longitudinal cohort component involving adolescents hospitalized for high risk of DSH, and a cross-sectional comparison with a control group of healthy adolescents recruited from primary care settings. It is aimed at identifying genetic, psychosocial, and clinical factors associated with suicidal behaviors and NSSI in adolescents. The study group is recruited from adolescents aged 12–19, admitted to the Intensive Child and Adolescent Psychiatry Unit in Ljubljana due to severe self-harm risk. Exclusion criteria include involuntary treatment, acute psychotic disorders, intellectual disability, severe physical or central nervous system illnesses and acute intoxication. The control group comprises adolescents of comparable age, recruited through regular scheduled health check-ups in Slovenia. Exclusion criteria include suicidality, severe mental disorder, a history of self-harm behavior in a first-degree relative, intellectual disability, severe physical or central nervous system illnesses and acute intoxication. Enrollment runs from February 1, 2023, to December 31, 2025. Participation is voluntary, requiring parental or guardian consent for those 14 or younger
Keywords: adolescents, deliberate self-harm, non-suicidal self-injury, suicidal behavior, intensive psychiatry, personality disorder, traumatic experience, genetics, epigenetics
Published in DiRROS: 24.02.2026; Views: 540; Downloads: 260
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Abstract: Introduction: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune necrotizing small vessel vasculitis, frequently resulting in severe renal manifestations such as rapidly progressive glomerulonephritis (AAV-GN). Monitoring disease activity and determining ongoing renal involvement remain significant clinical challenges due to the limitations associated with traditional biomarkers. This study focused on the potential of circulating microRNA (miRNA) as supplementary noninvasive biomarkers for disease activity in AAV-GN. Methods: This prospective follow-up study involved serum samples from 60 patients with biopsy-proven AAV-GN, collected at renal biopsy and at 3-, 6-, 12-, and 24-month intervals post-biopsy. Nine miRNAs (miR-21-3p, miR-30b/d/e-5p, miR-142-5p, miR-150-5p, miR-181a-5p, miR-181b-5p, and let-7a-5p) were selected based on the differential expressions in renal tissue and corresponding serum samples identified in the previous research phases. Expression analysis was performed using quantitative real-time polymerase chain reaction and correlated with disease activity based on the Birmingham Vasculitis Activity Score and other clinical parameters. Results: A significant correlation was identified between disease activity and the expression levels of the miR-30 family members and let-7a. Specifically, these miRNAs demonstrated consistent correlation patterns across follow-up samples independent of the time elapsed post-biopsy, with down-regulation correlating with the presence of active disease. Notably, the miRNA expression profile in partial remission appeared analogous to that of complete remission, suggesting that many patients categorized as having partial remission may, in fact, be considered in true clinical remission. Conclusion: This study supports serum miRNA profiling as an adjunct noninvasive biomarker for assessing disease activity in AAV-GN. Such an approach could provide complementary information alongside traditional biomarkers and refine the future management of AAV-GN. However, it is important to acknowledge that our actual study cohort was small due to challenging technical aspects of miRNA expression analysis in the serum. Therefore, further research with larger cohorts is required to validate these results and assess their clinical applicability.
Keywords: ANCA, vasculitis, glomerulonephritis, microRNA, biomarker, BVAS, epigenetics, follow-up
Published in DiRROS: 26.11.2025; Views: 551; Downloads: 344
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Abstract: Cultivar Désirée is an important model for potato functional genomics studies to assist breeding strategies. Here, we present a haplotype-resolved genome assembly of Désirée, achieved by assembling PacBio HiFi reads and Hi-C scaffolding, resulting in a high-contiguity chromosome-level assembly. We implemented a comprehensive annotation pipeline incorporating gene models and functional annotations from the Solanum tuberosum Phureja DM reference genome alongside RNA-seq reads to provide high-quality gene and transcript annotations. Additionally, we provide a genome-wide DNA methylation profile using Oxford Nanopore reads, enabling insights into potato epigenetics. The assembled genome, annotations, methylation and expression data are visualised in a publicly accessible genome browser, providing a valuable resource for the potato research community.
Keywords: cultivar Désirée, potato, functional genomics, genome assembly, annotation pipeline, DNA methylation, epigenetics
Published in DiRROS: 28.01.2025; Views: 1599; Downloads: 895
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Abstract: Background. Identifying the early genetic drivers can help diagnose glioma tumours in their early stages, before becoming malignant. However, there is emerging evidence that disturbance of epigenetic mechanisms also con- tributes to cell's malignant transformation and cancer progression. Long non-coding RNAs are one of key epigenetic modulators of signalling pathways, since gene expression regulation is one of their canonical mechanisms. The aim of our study was to search new gliomagenesis-specific candidate lncRNAs involved in epigenetic regulation. Patients and methods. We used a microarray approach to detect expression profiles of epigenetically involved lncRNAs on a set of 12 glioma samples, and selected LOC285758 for further qPCR expression validation on 157 glioma samples of different subtypes. To establish if change in expression is a consequence of epigenetic alterations we determined methylation status of lncRNA's promoter using MS-HRM. Additionally, we used the MLPA analysis for de- termining the status of known glioma biomarkers and used them for association analyses. Results. In all glioma subtypes levels of LOC285758 were significantly higher in comparison to normal brain reference RNA, and expression was inversely associated with promoter methylation. Expression substantially differs between astrocytoma and oligodendroglioma, and is elevated in higher WHO grades, which also showed loss of methylation. Conclusions. Our study revealed that lncRNA LOC285758 changed expression in glioma is methylation-dependent and methylation correlates with WHO malignancy grade. Methylation is also distinctive between astrocytoma I-III and other glioma subtypes and may thus serve as an additional biomarker in glioma diagnosis.
Keywords: glioma, epigenetics, methylation
Published in DiRROS: 03.06.2024; Views: 1395; Downloads: 951
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