1. Gene therapy of rare diseases as a milestone in medicine : overview of the field and report on initial experiences in SloveniaUrh Grošelj, Marko Kavčič, Ana Drole Torkar, Jan Kafol, Duško Lainšček, Roman Jerala, Matjaž Sever, Samo Zver, Gregor Serša, Maja Čemažar, Primož Strojan, Aleš Grošelj, Mojca Žerjav-Tanšek, Špela Miroševič, Simona Ivančan, Tomaž Prelog, David Gosar, Jasna Oražem, Matej Mlinarič, Sara Bertok, Jernej Kovač, Jana Kodrič, Saba Battelino, Marko Pokorn, Alojz Ihan, Janez Jazbec, Tadej Battelino, Damjan Osredkar, 2025, pregledni znanstveni članek Povzetek: 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.
Ključne besede: gene therapy, rare genetic diseases, Slovenia, CAR-T cells, cancer, immune gene therapy
Objavljeno v DiRROS: 04.12.2025; Ogledov: 28; Prenosov: 12
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2. The role of the MTUS1 gene in the development of left ventricular noncompaction cardiomyopathy : a case reportTevž Gorjanc, Jaka Šikonja, Ana Drole Torkar, Mojca Žerjav-Tanšek, Jernej Kovač, Sara Bertok, Maruša Debeljak, Zvezdana Dolenc-Stražar, Marija Meznarič, Jernej Mlakar, Mirko Topalović, Gorazd Mlakar, Tadej Battelino, Urh Grošelj, 2025, drugi znanstveni članki Ključne besede: left ventricular noncompaction cardiomyopathy, microtubule-associated scaffold protein 1 (MTUS1), whole-genome sequencing
Objavljeno v DiRROS: 02.12.2025; Ogledov: 49; Prenosov: 24
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3. Integrating genetic insights, technological advancements, screening, and personalized pharmacological interventions in childhood obesityRobert Šket, Barbara Slapnik, Primož Kotnik, Klementina Črepinšek, Barbara Čugalj Kern, Tine Tesovnik, Barbara Jenko Bizjan, Blaž Vrhovšek, Žiga Iztok Remec, Maruša Debeljak, Tadej Battelino, Jernej Kovač, 2025, pregledni znanstveni članek Povzetek: Childhood obesity is a significant global health challenge with rising prevalence over the past 50 years, affecting both immediate and long-term health outcomes. The increase in prevalence from 0.7% to 5.6% in girls and 0.9% to 7.8% in boys highlights the urgency of addressing this epidemic. By 2025, it is estimated that 206 million children and adolescents aged 5–19 years will be living with obesity. This review explores the complex interplay of genomics and genetics in pediatric obesity, transitioning from monogenic and polygenic obesity to epigenetics, and incorporating advancements in omics technologies. The evolutionary purpose of adiposity, systemic evaluation of hyperphagia, and the role of various genetic factors are discussed. Technological advancements in genotyping offer new insights and interventions. The integration of genetic screening into clinical practice for early identification and personalized treatment strategies is emphasized.
Ključne besede: hemophilia, wearable, Florio HAEMO, adherence, patient satisfaction
Objavljeno v DiRROS: 27.11.2025; Ogledov: 105; Prenosov: 59
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4. Unravelling genetic etiology of cerebral palsy : findings from a Slovenian pediatric cohortUla Arkar Silan, Ana Trebše, Jernej Kovač, Mihael Rogač, Anja Troha Gergeli, Robert Šket, Tina Bregant, David Neubauer, Borut Peterlin, Damjan Osredkar, 2025, izvirni znanstveni članek Povzetek: Introduction: Cerebral palsy (CP) is a permanent movement or postural disorder due to non-progressive injury to the developing brain, with recent research suggesting a genetic contribution in many patients. This study aimed to investigate the genetic etiology of CP in Slovene children without a previously suspected genetic cause or with prior negative genetic testing. Methods: All children born after 2003 from the Slovenian National Registry of Cerebral Palsy (SRCP) without an established genetic diagnosis were invited to participate in this cross-sectional study. Whole exome sequencing (WES) was conducted, followed by analysis of 110 CP-associated genes. Thirteen patients underwent additional family segregation by Sanger sequencing. Genetic findings were classified according to the ACMG guidelines. Results: The study included 136 children, of whom 68 (50%) were male. Spastic CP was identified in 85% of the participants, dyskinetic in 13%, and ataxic in 2%. Gross Motor Function Classification System (GMFCS) levels varied, with the majority (36%) classified as level I. Pathogenic variants, likely pathogenic variants, or ‘de novo’ variants of unknown significance (VUS) were identified in nine children (6.6%) in ATL1, CTNNB1, DYRK1, KMT2A, PROC, SPAST, ZC4H2, and ZSWIM6. Among these nine children, two had normal brain Magnetic Resonance Imaging (MRI) and three had an unsuspicious medical history. Conclusion: This study identified plausible, possible, or definite genetic etiologies in a cohort of children with CP. Apart from the exclusion of individuals with a previously established genetic diagnosis, no other selection criteria were applied, allowing for an inclusive assessment of genetic contributions within this population. With the advent of personalized medicine and genetic treatment, understanding the genetic underpinnings of CP is crucial for targeted therapy.
Ključne besede: cerebral palsy, genetic etiology, whole exome sequencing, gene therapy, CTNNB1
Objavljeno v DiRROS: 21.11.2025; Ogledov: 142; Prenosov: 61
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5. Sex differences in cholesterol levels among prepubertal childrenJan Kafol, Mia Becker, Barbara Čugalj Kern, Jaka Šikonja, Matej Mlinarič, Katarina Sedej, Matej Kafol, Ana Drole Torkar, Jernej Kovač, Tadej Battelino, Urh Grošelj, 2025, izvirni znanstveni članek Povzetek: Background and aims: Sex differences in cholesterol levels are well documented in adults and adolescents, but limited data exist for prepubertal children. This study aimed to evaluate innate sex differences in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels among prepubertal children, both in the general population and among those with familial hypercholesterolemia (FH). Methods: This cross-sectional study used data from Slovenia’s Universal FH Screening Program. Two populationbased random samples of children undergoing routine cholesterol screening at age 5 years were included from 2014 (N = 3412) and 2023 (N = 4182). In addition, a referred cohort from the Slovenian Hypercholesterolemia Registry (n = 1160, aged <10 years) who underwent genetic testing was analyzed. Results: In both the 2014 and 2023 cohorts, girls had significantly higher TC levels than boys (median difference: 0.10–0.11 mmol/L; p < 0.05). Among FH-negative children in the Registry, girls had on average 0.14 mmol/L higher TC and 0.13 mmol/L higher LDL-C than boys (both p < 0.05). No sex differences were observed in FHpositive children (p = 0.83 for TC; p = 0.82 for LDL-C). In the overall Registry cohort, after adjusting for FH status, girls had 0.11 mmol/L higher TC and 0.10 mmol/L higher LDL-C (both p < 0.05). Conclusion: Prepubertal girls have modestly higher TC and LDL-C than boys, a difference not observed in prepubertal FH-positive children, suggesting that the presence of a pathogenic FH variant may override innate physiological differences in lipid metabolism. These findings support universal early cholesterol screening and suggest that sex-specific reference values may improve early cardiovascular risk assessment in prepubertal FHnegative children.
Ključne besede: sex differences, prepubertal children, total cholesterol, low-density lipoprotein cholesterol, familial hypercholesterolemia
Objavljeno v DiRROS: 17.11.2025; Ogledov: 122; Prenosov: 58
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6. Enhanced oral glucose tolerance test for early detection of insulin resistance and metabolic complications in children with obesityUrh Grošelj, Jan Kafol, Jaka Šikonja, Matej Mlinarič, Robert Šket, Žiga Iztok Remec, Jernej Kovač, Ana Drole Torkar, Jasna Šuput, Barbka Repič-Lampret, Tadej Battelino, Primož Kotnik, 2025, izvirni znanstveni članek Povzetek: Background and aims: Early detection of insulin resistance (IR) and obesity-related complications is crucial for preventing type 2 diabetes. This study aimed to identify dynamic metabolic biomarkers for more precise early detection of IR and metabolic abnormalities. Methods: This cross-sectional cohort study evaluated IR and metabolic biomarkers in 403 children with obesity (median age 13.18 years, 51.3 % female, 98.5 % with obesity) using an enhanced oral glucose tolerance test (eOGTT). IR was assessed via four indices, with the Matsuda Insulin Sensitivity Index (ISI-M) used as the primary measure. Participants were stratified into quartiles based on ISI-M. Results: Participants with the highest IR (Q1) were older (p = 0.002), had a higher body mass index, were in a more advanced pubertal stage (p < 0.001), and had significantly elevated glucose and insulin levels (p < 0.001 for both) compared to the most insulin sensitive (Q4), with significant differences observed across all quartiles (p < 0.050 for all). Insulin at 120 min demonstrated excellent diagnostic accuracy for IR (AUC=0.958). Triglyceride levels in Q1 showed minimal decline during the eOGTT, while greater declines were observed with increasing insulin sensitivity (p = 0.002 across quartiles), suggesting that a lack of decline in triglycerides may help identify IR. High-sensitivity C-reactive protein levels increased with IR (p = 0.024). Baseline beta-hydroxybutyrate levels were highest in the Q4 and showed the greatest absolute decrease during the eOGTT, compared to Q1 (p < 0.001 for both). Conclusions: We validated established IR markers in children with obesity, while demonstrating that eOGTT may offer improved characterization and earlier identification of those at risk for metabolic complications.
Ključne besede: insulin resistance, oral glucose tolerance test, OGTT, metabolic complications, screening, children, adolescents, obesity
Objavljeno v DiRROS: 11.11.2025; Ogledov: 185; Prenosov: 73
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7. 20. maj, svetovni dan čebelJernej Kovač, Helena Gašperlin, Danilo Bevk, Peter Kozmus, druge monografije in druga zaključena dela Povzetek: Za jutrišnjo hrano v svetu Čebele in drugi opraševalci so zelo pomembni za obstoj človeštva, saj bistveno prispevajo k varnosti preskrbe s hrano v svetu. Tretjina svetovne proizvodnje hrane oziroma vsaka tretja žlica hrane je odvisna od opraševanja, pri katerem imajo čebele najpomembnejšo vlogo. Visoko hranilni proizvodi, kot so med, matični mleček in cvetni prah, prav tako povečujejo hranilno vrednost živil. Živila, ki so odvisna od opraševalcev, prispevajo k zdravi prehrani, saj so bogat vir nujno potrebnih hranil.
Ključne besede: čebelarstvo
Objavljeno v DiRROS: 04.09.2024; Ogledov: 678; Prenosov: 517
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