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Povzetek: Determining variant TPMT alleles to predict patient response to thiopurine therapy represents one of the first successful implementations of pharmacogenomics in clinical practice. However, despite the TPMT-adjusted thiopurine dosing, some TPMT wild-type patients still exhibit toxicity at standard doses. Over the past decade, the pharmacogene NUDT15 has emerged as a significant co-modulator of thiopurine therapy. Initially, NUDT15 was considered important predominantly in Asian populations, but recent studies have highlighted its relevance in European populations as well. To evaluate the pharmacogenetic significance of NUDT15 in the Slovenian population, we sequenced extended regions of exon 1 and exon 3 in 109 healthy individuals and 37 patients with acute lymphoblastic leukemia. We identified eight variants, including one with established clinical significance (allele *3) and one extremely rare variant (Chr13 at 48045861; GRCh38, NC_000013.11). The frequencies of most previously described variants in both the general population and in the ALL cohort were consistent with those reported in other European populations, except for rs45465203, which was less frequent in the Slovenian population. None of the variants, except for NUDT15*3, were associated with cumulative thiopurine doses in ALL patients. However, these variants warrant further investigation in larger ALL cohorts.
Ključne besede: 6-mercaptopurine, acutelymphoblastic leukemia, dose reduction, minorallele frequency, NUDT15, population genetics, thiopurines
Objavljeno v DiRROS: 16.06.2026; Ogledov: 169; Prenosov: 167
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Povzetek: Background: Multiple familial hypercholesterolemia (FH) screening strategies are recommended, but how they work together within a population remains poorly understood. Here, we aimed to compare the characteristics of children diagnosed through a universal screening program with those of adults identified through opportunistic screening. Methods: In this retrospective cross-sectional study, we analyzed the clinical and genetic characteristics of children and adults with genetically confirmed heterozygous FH (HeFH). Results: Out of 442 children and 299 adults with a definite or probable FH based on clinical criteria, 39 (13.0%) adults and 197 (44.6%) children had also a genetic HeFH. FH causative variants were present in low-density lipoprotein receptor (LDLR) in 159 (67.4%) patients and in apolipoprotein B (APOB) in 77 (32.6%) patients. The combined screening approach identified 44 disease-causing variants, of which 2 and 25 were unique to the adult and pediatric cohort, respectively. The proportion of children with missense variants was significantly higher (172 [87.3%] vs. 27 [69.2%]; p = 0.005), whereas the proportion of termination variants was significantly lower (20 [10.2%] vs. 11 [28.2%]; p = 0.002) compared to the adult group. Adults had higher adjusted low-density lipoprotein cholesterol compared to children. Conclusions: Our study suggests that opportunistic adult screening identifies more severe FH phenotypes, while universal pediatric screening detects milder cases.
Ključne besede: familial hypercholesterolemia, adults, children, genetics, universal screening, opportunistic screening
Objavljeno v DiRROS: 01.06.2026; Ogledov: 175; Prenosov: 174
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Povzetek: Background Global developmental delay (GDD) is a common pediatric disorder that affects up to 3% of children. Due to the heterogeneous etiology of GDD, diagnostic procedures and algorithms are complex and diverse. The aim of our study was to investigate the diagnostic yield of genetic, metabolic, and imaging studies in establishing the etiology of unexplained GDD (UGDD). Methods In this retrospectively observational study, we examined the medical records of all children diagnosed with UGDD at the Department of Pediatric Neurology, University Medical Centre Ljubljana, Slovenia, between January and December 2019. We evaluated the effectiveness of various genetic, metabolic, and magnetic resonance imaging (MRI) tests in identifying the underlying cause of GDD. Additionally, we assessed subgroups of patients to determine whether any of the studied tests were particularly beneficial based on their clinical symptoms. Results A total of 123 patients met the inclusion criteria, with a median age of 4.3 years (range, 0–16 years), of which 71 (57.7%) were males. Genetic diagnosis was established in 47.1% (58/123) of patients. Metabolic laboratory testing did not identify a metabolic disease in any of the tested participants (114/123) and MRI was critical for diagnosis in only 1/81 (1.2%) patient. Conclusion Our findings strongly suggest that genetic testing surpasses MRI and metabolic testing in establishing the etiology of UGDD in a pediatric neurology outpatient setting. This information will help guide the diagnostic evaluation of these children
Ključne besede: unexplained global developmental delay, diagnostic yield, genetics, MRI, metabolic screening
Objavljeno v DiRROS: 16.04.2026; Ogledov: 262; Prenosov: 260
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Povzetek: Sarcoidosis is a systemic disorder driven by genetic predisposition, environmental exposures, and immune dysregulation, resulting in the formation of noncaseating granulomas across multiple organs. In cardiac sarcoidosis (CS), immune cell infiltration of the myocardium, epicardium, and endocardium may lead to conduction disturbances, ventricular arrhythmias, and heart failure. While overt cardiac involvement was historically considered rare, affecting only 5% of sarcoidosis patients, the wider availability and improved sensitivity of contemporary cardiac imaging have revealed a substantially higher burden, with cardiac involvement reaching up to 55% in selected, systematically screened populations. Current diagnostic approaches for CS, including endomyocardial biopsy (EMB), cardiovascular magnetic resonance (CMR), and fluorine-18 fluorodeoxyglucose–positron emission tomography (FDG-PET), offer valuable insights but are restricted by high costs, invasiveness, and limited sensitivity and specificity. These challenges, together with the disproportionate contribution of cardiac involvement to sarcoidosis-related mortality, underscore the need for innovative, non-invasive, and widely accessible diagnostic strategies. Emerging evidence suggests that novel serum biomarkers and genomic studies hold promise for transforming the diagnostic landscape of CS. Biomarkers may provide accessible, cost-effective tools to complement established diagnostic methods, while genetic insights could identify individuals at higher risk for cardiac involvement and stratify patients based on disease phenotype. This review examines current evidence on serum biomarkers and genetic studies in CS diagnosis, identifies critical knowledge gaps, and proposes future directions aimed at advancing diagnostic precision and improving clinical outcomes.
Ključne besede: biomarker, genetics, heart, sarcoidosis, therapy
Objavljeno v DiRROS: 26.03.2026; Ogledov: 246; Prenosov: 167
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Povzetek: 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
Ključne besede: adolescents, deliberate self-harm, non-suicidal self-injury, suicidal behavior, intensive psychiatry, personality disorder, traumatic experience, genetics, epigenetics
Objavljeno v DiRROS: 24.02.2026; Ogledov: 473; Prenosov: 236
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