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Background Long QT syndrome (LQTS) is one of the most common inherited cardiac arrhythmias associated with sudden cardiac death worldwide. Despite the widespread implementation of next-generation sequencing, its diagnostic value remains limited due to challenges in interpreting the clinical significance of the identified variants. Since LQTS is rare and underreported in Baltic region, studies on small populations are valuable for expanding current knowledge on this rare cardiac channelopathy. Our aim was to evaluate the diagnostic yield of genetic testing and clinical manifestations of the disease in paediatric patients assessed for LQTS in Lithuania. Results The phenotypic spectrum of LQTS among the cohort was notably heterogeneous, with more than half of the asymptomatic patients at the time of genetic testing. The overall diagnostic yield was 22%. The majority of pathogenic or likely pathogenic variants were detected in the KCNQ1 gene, with 17% of these categorised as high-risk for arrhythmic events. Individuals harbouring pathogenic or likely pathogenic variants showed significantly prolonged corrected QT (QTc) intervals in comparison to those without such variants. Conclusions Less stringent referral criteria may reduce the diagnostic yield of genetic testing for LQTS. In our cohort, 17% of patients with 1 type LQTS had genetic variants located in regions associated with elevated arrhythmic risk. This knowledge should be considered as part of their individualised care plans. Furthermore, the identification of multiple variants of uncertain significance highlights the ongoing need for enhanced interpretive frameworks to integrate complex genetic findings into routine clinical decision-making.

Cannabidiol (CBD) has potential for treating obesity-induced inflammation; thus, we studied the influence of CBD on the accumulation of lipid precursors of inflammation, the, enzymes, and cytokine levels in the subcutaneous (SAT) and visceral adipose tissue (VAT) of animals with obesity-induced early-stage inflammation. Our experiment was performed on rats fed a high-fat (HFD) or control diet, which received CBD or its vehicle. The accumulation and composition of lipid fractions were assessed via gas‒liquid chromatography, whereas the expression of inflammatory pathway enzymes and the cytokine content were evaluated via Western blot or multiplexing, respectively. In addition to selective changes in the content of cytokines, the administration of CBD to HFD-fed rats also decreased the deposition of all the lipid fractions in VAT, whereas in SAT, only the free fatty acid and diacylglycerol fractions were affected. Moreover, CBD reduced the deposition of arachidonic acid and the expression of enzymes associated with the synthesis of lipid precursors of inflammation in both the SAT and VAT of HFD-fed rats. Although the data revealed the beneficial influence of CBD on lipid precursors of inflammation metabolism in both fat depots, more pronounced changes were observed in VAT, which is a tissue that is more predisposed to metabolic disease development.

Background and Objectives: Pathogenic variants in the PAX2 gene have been associated with a spectrum of eye and kidney disorders, ranging from papillorenal syndrome (known as renal coloboma syndrome) to isolated nephrosis without kidney morphological anomalies (focal segmental glomerulosclerosis), inherited in an autosomal dominant manner. However, due to the growing number of reports of pathogenic variants in the PAX2 gene, it is observed that genotype–phenotype correlation is not always consistent. We present patients from two unrelated families with PAX2 pathogenic variants c.685C>T and c.250G>A, highlighting the diverse phenotypic expression of PAX2-related disorders. Materials and Methods: We analyzed clinical and genetic data from two families who were tested for genomic abnormalities using targeted next-generation sequencing and Sanger sequencing for segregation analysis. Results: In Family A, a 27-year-old male presented with chronic kidney disease stage 3, proteinuria, and multicystic kidney dysplasia diagnosed at 11 years old. An ophthalmologic examination revealed bilateral optic nerve dysplasia. In Family B, a 6-year-old female and her 4-year-old sister were clinically diagnosed with renal hypoplasia, while their 36-year-old father presented with chronic kidney disease stage 3, focal segmental glomerulosclerosis, and optic disc pits. Genetic analysis identified a heterozygous PAX2 pathogenic variant c.685C>T, p.(Arg229*), in Family A and a heterozygous PAX2 pathogenic variant c.250G>A, p.(Gly84Ser) in Family B. Conclusions: The literature and our data further support that the same PAX2 variants may cause diverse kidney and ocular phenotypes among unrelated families and within the same family. Due to variable expressivity, a wide range of clinical manifestations of rare hereditary kidney diseases are still underdiagnosed, and a multidisciplinary approach is required to detect extrarenal signs of PAX2-related disorder.

People living with rare diseases (PLWRD) still face huge unmet needs, in part due to the fact that care systems are not sufficiently aligned with their needs and healthcare workforce (HWF) along their care pathways lacks competencies to efficiently tackle rare disease-specific challenges. Level of rare disease knowledge and awareness among the current and future HWF is insufficient. In recent years, many educational resources on rare diseases have been developed, however, awareness of these resources is still limited and rare disease education is still not sufficiently taken into account by some crucial stakeholders as academia and professional organizations. Therefore, there is a need to fundamentally rethink rare disease education and HWF development across the whole spectrum from students to generalists, specialists and experts, to engage and empower PLWRD, their families and advocates, and to work towards a common coherent and complementary strategy on rare disease education and training in Europe and beyond. Special consideration should be also given to the role of nurse coordinators in care coordination, interprofessional training for integrated multidisciplinary care, patient and family-centered education, opportunities given by digital learning and fostering of social accountability to enforce the focus on socially-vulnerable groups such as PLWRD. The strategy has to be developed and implemented by multiple rare disease education and training providers: universities, medical and nursing schools and their associations, professional organizations, European Reference Networks, patient organizations, other organizations and institutions dedicated to rare diseases and rare cancers, authorities and policy bodies.

Background Mitochondrial Diseases (MDs) are a diverse group of neurometabolic disorders characterized by impaired mitochondrial oxidative phosphorylation and caused by pathogenic variants in more than 400 genes. The implementation of next-generation sequencing (NGS) technologies helps to increase the understanding of molecular basis and diagnostic yield of these conditions. The purpose of the study was to investigate diagnostic and genotypic spectrum in patients with suspected MD. The comprehensive analysis of mtDNA variants using Sanger sequencing was performed in the group of 83 unrelated individuals with clinically suspected mitochondrial disease. Additionally, targeted next generation sequencing or whole exome sequencing (WES) was performed for 30 patients of the study group. Results The overall diagnostic rate was 21.7% for the patients with suspected MD, increasing to 36.7% in the group of patients where NGS methods were applied. Mitochondrial disease was confirmed in 11 patients (13.3%), including few classical mitochondrial syndromes (MELAS, MERRF, Leigh and Kearns-Sayre syndrome) caused by pathogenic mtDNA variants (8.4%) and MDs caused by pathogenic variants in five nDNA genes. Other neuromuscular diseases caused by pathogenic variants in seven nDNA genes, were confirmed in seven patients (23.3%). Conclusion The wide spectrum of identified rare mitochondrial or neurodevelopmental diseases proves that MD suspected patients would mostly benefit from an extensive genetic profiling allowing rapid diagnostics and improving the care of these patients.

Human athletic performance is a complex phenotype influenced by environmental and genetic factors, with most exercise-related traits being polygenic in nature. The aim of this article is to outline some of the challenge faced by sports genetics as this relatively new field moves forward. This review summarizes recent advances in sports science and discusses the impact of the genome, epigenome and other omics (such as proteomics and metabolomics) on athletic performance. The article also highlights the current status of gene doping and examines the possibility of applying genetic knowledge to predict athletes’ injury risk and to prevent the rare but alarming occurrence of sudden deaths during sporting events. Future research in large cohorts of athletes has the potential to detect new genetic variants and to confirm the previously identified DNA variants believed to explain the natural predisposition of some individuals to certain athletic abilities and health benefits. It is hoped that this article will be useful to sports scientists who seek a greater understanding of how genetics influences exercise science and how genomic and other multi-omics approaches might support performance analysis, coaching, personalizing nutrition, rehabilitation and sports medicine, as well as the potential to develop new rationale for future scientific investigation.

Background and Objectives: Cuticular drusen are a rare form of early-onset drusen maculopathy, which falls within the spectrum of age-related macular degeneration. Previous research suggests that cuticular drusen can result from monogenic inheritance of pathogenic variants in the complement factor H coding CFH gene. These variants impair regulation of the alternative complement pathway, leading to increased central retinal inflammation, progressive tissue damage, and ultimately, vision loss. This study aims to assess the pathogenic potential of the variant NM_000186.4(CFH):c.1318C>T, previously classified as a variant of unknown significance. Materials and Methods: Eight individuals from three generations of a single family underwent ophthalmologic evaluation, including biomicroscopy, ophthalmoscopy, optical coherence tomography, and optical coherence tomography angiography. Subsequently, whole-exome sequencing of the proband‘s DNA sample was performed. Sanger sequencing was used to validate the whole-exome sequencing results and to assess segregation of the identified variant in the family. The individuals’ clinical, instrumental, and genetic data were collected and stored in the database iGENLIT. Results: the heterozygous NM_000186.4(CFH):c.1318C>T variant was detected in six family members. Of these, five have been clinically diagnosed with cuticular drusen. Three affected individuals are currently in their 40s and maintain good visual acuity. In two family members, the drusen progressed to choroidal neovascularization, fibrosis, and atrophy, resulting in profound visual loss at the ages of 54 and 62. One 21-year-old individual also carries the variant, but currently shows no evidence of drusen, likely due to age. Conclusion: In this study, we demonstrated a genotype–phenotype relationship in individuals with the NM_000186.4(CFH):c.1318C>T variant, which suggests its pathogenic role in the development of cuticular drusen and associated complications.

Intracerebral hemorrhage (ICH) is a devastating type of stroke, frequently resulting in unfavorable functional outcomes. Up to 15% of stroke patients experience ICH and approximately half of those have a lethal outcome within a year. Considering the huge burden of ICH, timely prevention and optimized treatment strategies are particularly relevant. Nevertheless, ICH management options are quite limited, despite thorough research. More and more trials highlight the importance of the genetic component in the pathogenesis of ICH. Apart from distinct monogenic disorders of familial character, mostly occurring in younger subjects, there are numerous polygenic risk factors, such as hypertension, neurovascular inflammation, disorders of lipid metabolism and coagulation cascade, and small vessel disease. In this paper we describe gene-related ICH types and underlying mechanisms. We also briefly discuss the emerging treatment options and possible clinical relevance of the genetic findings in ICH management. Although existing data seems of more theoretical and scientific value so far, a growing body of evidence, combined with rapidly evolving experimental research, will probably serve clinicians in the future.

Background Congenital anomalies represent a major cause of childhood morbidity and disability, imposing long-term health, social, and financial challenges. While medical expenditures are relatively well-documented, evidence on the broader financial and social impact on families—particularly in Central and Eastern Europe—remains limited. Accordingly, this study aimed to quantify the economic burden associated with congenital anomalies from a caregiver perspective. Methods A cross-sectional, questionnaire-based study was conducted in Lithuania in 2023 among 160 caregivers of children aged 5–18 years diagnosed with congenital anomalies. Participants were grouped by the number of affected organ systems to reflect the increasing disease complexity. Using standardized cost-of-illness methodology and both the human capital and opportunity cost approaches, we estimated annual direct medical and non-medical, indirect, and informal care costs. Results Families experienced a substantial and multidimensional financial burden that intensified with disease severity. The annual indirect cost, mainly reflecting productivity losses, represented the largest component of the total economic burden, with a median of €7,566 overall and €12,965 in the most severely affected families. Out-of-pocket payments were also considerable, with a median of €2,040 per year; in the most severe group they exceeded 20% of monthly household income for 42% of families. The economic value of informal care represented a smaller yet meaningful portion of total costs (median €1,967), increasing more than fivefold between the mildest and most severe groups. Conclusions Congenital anomalies place a substantial economic burden on families, extending far beyond healthcare expenses. These findings highlight the need for policies that improve financial protection, support caregivers’ labor market participation, and acknowledge the economic value of informal care within health and welfare systems. Key points • Families raising children with congenital anomalies in Lithuania face substantial financial, productivity, and informal caregiving burdens, which increase sharply with condition severity. • The largest pressures arise from reduced work participation, high out-of-pocket expenses, and extensive unpaid caregiving time. • These findings highlight the need for stronger financial protection and caregiver support, particularly for families of children with complex or multisystem anomalies.

Background Kearns‐Sayre syndrome (KSS) is a rare multisystem mitochondrial disorder characterized by onset before 20 years of age and a typical clinical triad: progressive external ophthalmoplegia, pigmentary retinopathy and cardiac conduction anomalies. In most cases KSS is caused by spontaneous heteroplasmic single large‐scale mitochondrial DNA (mtDNA) deletions. Long‐range polymerase chain reaction (LR‐PCR), next generation sequencing (NGS) and multiplex ligation‐dependent probe amplification (MLPA) are the most widely applied methods for the identification of mtDNA deletions. Here, we report the case of 20‐year‐old male who presented with classic Kearns‐Sayre syndrome, confirmed by novel 5,9 kb mtDNA deletion. Methods and results LR‐PCR and MLPA methods were applied to identify the mitochondrial DNA deletion for the patient, but the results were conflicting. Molecular analysis using primer walking and Sanger sequencing identified a novel 5888 base pairs mtDNA deletion (NC_012920.1:m.6069_11956del) with CAAC nucleotides repeat sequence at the breakpoints. Conclusion Our study enriched the mtDNA variation spectrum associated with KSS and demonstrated the importance of choosing relevant molecular genetic methods. Novel 5,9 kb mtDNA deletion was identified for a 20‐year‐old male who presented with classic Kearns‐Sayre syndrome. Different molecular genetic methods were applied to identify the mitochondrial DNA deletion, but obtaining conflicting research results demonstrated the importance of choosing relevant molecular genetic methods.