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Abstract: Optical genome mapping (OGM) is a novel method enabling the detection of structural genomic variants. The method is based on the laser image acquisition of single, labeled, high-molecular-weight DNA molecules and can detect structural genomic variants such as translocations, inversions, insertions, deletions, duplications, and complex structural rearrangements. We aim to present our experience with OGM at the Clinical Institute of Genomic Medicine, University Medical Centre Ljubljana, Slovenia. Since its introduction in 2021, we have used OGM for the testing of facioscapulohumeral muscular dystrophy 1, characterization and resolution of variants identified by other technologies such as microarrays, exome and genome next-generation sequencing, karyotyping, as well as testing of rare disease patients in whom no genetic cause could be identified using these methods. We present an example family case of two previously undiagnosed male siblings with an overlapping clinical presentation of thrombocytopenia, obesity, and presacral teratoma. After karyotyping, microarray analysis and next-generation sequencing, by using OGM, a maternally inherited cryptic translocation t(X;18)(q27.1;q12.2) was identified in both brothers. Despite an extended segregation analysis, based on strictly applied ACMG criteria and ClinGen guidelines, the identified translocation remains a variant of unknown significance. Despite the remaining limitations of OGM, which will hopefully be resolved by improvements in databases of known benign SV variation and the establishment of official guidelines on the clinical interpretation of OGM variants, our work highlights the complexity of the diagnostic journey, including this novel method, in rare disease cases.
Keywords: optical genome mapping, OGM, structural variants, SV, genomic variants, rare disease genetic testing
Published in DiRROS: 04.12.2025; Views: 119; Downloads: 52
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Abstract: Purpose: This study aimed to assess the efficacy of Janus kinase inhibitors (JAK-i) in the treatment of refractory isolated non-infectious uveitis. Case presentation: We examined a case series involving three patients with isolated non-infectious uveitis, who were managed between December 2019 and December 2023 at The Eye Hospital, University Medical Centre Ljubljana. The JAK-i therapy was initiated due to the patients’ unresponsiveness to disease-modifying antirheumatic drugs. Outcomes: In our case series, two patients presented with anterior and intermediate uveitis, one with posterior uveitis. None of the patients had any associated systemic disease. After the initiation of JAK-I therapy, all the patients achieved remission lasting for more than 1 year. No significant side effects were observed in any of the patients throughout a mean follow-up period of 31.6 months (range, 16–55 months). Conclusion: In this report, we present three cases of refractory isolated non-infectious uveitis successfully treated with JAK-i. This is the first report on the use of baricitinib and upadacitinib in this context. Our findings suggest that alternative use of JAK-i, apart from tofacitinib alone, may be an effective treatment option for such patients.
Keywords: JAK inhibitors, uveitis, biologics
Published in DiRROS: 04.12.2025; Views: 76; Downloads: 34
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Abstract: ewborn screening for Phenylketonuria enables early detection and timely treatment with a phenylalanine-restricted diet to prevent severe neurological impairment. Although effective and in use for 60 years, screening, diagnostic, and treatment practices still vary widely across countries and centers. To evaluate the Phenylketonuria newborn screening practices internationally, we designed a survey with questions focusing on the laboratory aspect of the screening system. We analyzed 24 completed surveys from 23 countries. Most participants used the same sampling age range of 48–72 h; they used tandem mass spectrometry and commercial non-derivatized kits to measure phenylalanine (Phe), and had non-negative cut-off values (COV) set mostly at 120 µmol/L of Phe. Participants mostly used genetic analysis of blood and detailed amino acid analysis from blood plasma as their confirmatory methods and set the COV for the initiation of dietary therapy at 360 µmol/L of Phe. There were striking differences in practice as well. While most participants reported a 48–72 h range for age at sampling, that range was overall quite diverse Screening COV varied as well. Additional screening parameters, e.g., the phenylalanine/tyrosine ratio were used by some participants to determine the screening result. Some participants included testing for tetrahydrobiopterin deficiency, or galactosemia in their diagnostic process. Results together showed that there is room to select a best practice from the many practices applied. Such a best practice of PKU-NBS parameters and post-screening parameters could then serve as a generally applicable guideline.
Keywords: phenylketonuria, newborn, neonatal, screening, international, survey, laboratory, methods, cut-off
Published in DiRROS: 04.12.2025; Views: 122; Downloads: 57
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Abstract: Gene therapy has transitioned from a long-awaited promise to a clinical reality, offering transformative treatments for rare congenital diseases and certain cancers, which have a significant impact on patients’ lives. Current approaches focus on gene replacement therapy, either in vivo or ex vivo, mostly utilizing viral vectors to deliver therapeutic genes into target cells. However, refining these techniques is essential to overcome challenges and complications associated with gene therapy to ensure long-term safety and efficacy. Slovenia has witnessed significant advancements in this field since 2018, marked by successful gene therapy trials and treatments for various rare diseases. Significant strides have been made in the field of gene therapy in Slovenia, treating patients with spinal muscular atrophy and rare metabolic disorders, including the pioneering work on CTNNB1 syndrome. Additionally, immune gene therapy, exemplified by IL-12 adjuvant therapy for cancer, has been a focus of research in Slovenia. Through patient-centred initiatives and international collaborations, researchers in Slovenia are advancing preclinical research and clinical trials, paving the way for accessible gene therapies. Establishing clinical infrastructure and genomic diagnostics for rare diseases is crucial for gene therapy implementation. Efforts in this regard in Slovenia, including the establishment of a Centre for Rare Diseases, Centre for the Technologies of Gene and Cell Therapy, and rapid genomic diagnostics, demonstrate a commitment to comprehensive patient care. Despite the promises of gene therapy, challenges remain, including cost, distribution, efficacy, and long-term safety. Collaborative efforts are essential to address these challenges and ensure equitable access to innovative therapies for patients with rare diseases.
Keywords: gene therapy, rare genetic diseases, Slovenia, CAR-T cells, cancer, immune gene therapy
Published in DiRROS: 04.12.2025; Views: 128; Downloads: 112
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Abstract: We revisit the decay rate of the electroweak vacuum in the standard model with the full one-loop prefactor. We focus on the gauge degrees of freedom and derive the degeneracy factors appearing in the functional determinant using group theoretical arguments. Our treatment shows that the transverse modes were previously overcounted, so we revise the calculation of that part of the prefactor. The new result modifies the gauge fields’ contribution by 6% and slightly decreases the previously predicted lifetime of the electroweak vacuum, which remains much longer than the age of the Universe. Our discussion of the transverse mode degeneracy applies to any calculation of functional determinants involving gauge fields in four dimensions.
Published in DiRROS: 04.12.2025; Views: 118; Downloads: 40
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