Browsing by Author "Novaković, Ivana (6603235567)"

[No abstract available]

[No abstract available]

Background/Aim. Duchenne muscular dystrophy (DMD) and its allelic form Becker muscular dystrophy (BMD) are X-linked diseases that affect males, characterized by progressive muscle and cardiopulmonary weakness, especially in DMD as a severe form of the disease. They result from mutations in the dystrophin gene, and the most common changes are large intragenic deletions and duplications (80%). One third of patients have de novo mutation and 2/3 of the mothers are estimated as carriers. The aim of the study was to analyze the frequency of duplications versus deletions in the dystrophin gene in patients with dystrophinopathies, as well as to analyze the phenotypic effect of large mutations obtained and to determine the carrier status of female relatives in probands with duplications. Methods. We examined 22 DMD and 35 BMD unrelated patients and 6 female relatives of the probands where duplications were found. We used polymerase chain reaction (PCR) and multiplex ligation-dependent probe amplification (MLPA) methods, according to the protocol, to detect or confirm mutations in probands and female carriers. Results. In probands, there were 34 (59.6%) large deletions (mostly affected exons 44–60) and 6 (10.5%) large duplications in 4 DMD and 2 BMD patients. Also, duplications were found in 3 out of 4 (75%) tested mothers. The distribution of duplications was heterogeneous, affecting N-terminal and central rod domain, and included more exons, except for one DMD patient who had duplication of exon 2. An exception from the Monaco rule was present in 9.5% of DMD and 15.8% of BMD probands, i.e. in 12.5% of DMD/BMD cases. Conclusion. In 57 DMD/BMD probands, we found 59.6% of large deletions and 10.5% of large duplications. The most affected region of the DMD gene was the central rod domain. An exception to Monaco's rule was present in 12.5% of DMD/BMD cases. Three out of 4 examined proband's mothers were confirmed as carriers. © 2020 Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved.

Background: Biallelic pathogenic variants in the ANO10 gene cause autosomal recessive progressive ataxia (ATX-ANO10). Methods: Following the MDSGene protocol, we systematically investigated genotype–phenotype relationships in ATX-ANO10 based on the clinical and genetic data from 82 published and 12 newly identified patients. Results: Most patients (>80%) had loss-of-function (LOF) variants. The most common variant was c.1150_1151del, found in all 29 patients of Romani ancestry, who had a 14-year earlier mean age at onset than patients homozygous for other LOF variants. We identified previously undescribed clinical features of ATX-ANO10 (e.g., facial muscle involvement and strabismus) suggesting the involvement of brainstem pathology, and we propose a diagnostic algorithm that may aid clinical ATX-ANO10 diagnosis. Conclusions: The early disease onset in patients with c.1150_1151del may indicate the existence of genetic/environmental disease-modifying factors in the Romani population. Our findings will inform patient counseling and may improve our understanding of the disease mechanism. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: Biallelic pathogenic variants in the ANO10 gene cause autosomal recessive progressive ataxia (ATX-ANO10). Methods: Following the MDSGene protocol, we systematically investigated genotype–phenotype relationships in ATX-ANO10 based on the clinical and genetic data from 82 published and 12 newly identified patients. Results: Most patients (>80%) had loss-of-function (LOF) variants. The most common variant was c.1150_1151del, found in all 29 patients of Romani ancestry, who had a 14-year earlier mean age at onset than patients homozygous for other LOF variants. We identified previously undescribed clinical features of ATX-ANO10 (e.g., facial muscle involvement and strabismus) suggesting the involvement of brainstem pathology, and we propose a diagnostic algorithm that may aid clinical ATX-ANO10 diagnosis. Conclusions: The early disease onset in patients with c.1150_1151del may indicate the existence of genetic/environmental disease-modifying factors in the Romani population. Our findings will inform patient counseling and may improve our understanding of the disease mechanism. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background/Aim: Peroxisome proliferator-activated receptor gamma (PPARγ) be-longs to a family of nuclear hormone receptors and ligand-activated transcription factors. PPARG gene is expressed in many tissues including adipose tissue where it plays a crucial role in differentiation of adipocyte, insulin resistance, blood glucose levels and lipid metabolism. The aim of the study was to examine the association of rs3856806 polymorphism with the body mass index (BMI), fasting glucose levels and lipid parameters in Serbian adolescents. Methods: This research included 287 adolescents of both genders (143 boys and 144 girls), 14-15 years of age. Genotype detection was done by polymerase chain reaction-restriction fragment length polymorphism (RFLP) assay. Results: Results showed statistically significant difference in terms of fasting glucose levels among girls (p = 0.013) depending on their genotype. Female carriers of CC genotype had significantly higher level of fasting glucose levels. Also, results showed that in the group of overweight and obese girls, carriers of CT or TT gen-otype had statistically significant lower values of HDL cholesterol compared to girls-carriers of CC genotype (p = 0.000). However, this result was not confirmed by multiple regression analysis. Statistically significant association of rs3856806 polymorphism was not observed with BMI nor with other lipid parameters. Conclusion: This polymorphism is associated with fasting glucose level and HDL cholesterol among girls. To draw definite conclusions, further research should be conducted including non-genetic factors and other polymorphisms among this gene. © 2021 Vidović et al.

Background. Influence of TMPRSS6 A736V and HFE (C282Y and H63D) polymorphisms on serum hepcidin-25 levels and iron status parameters in end-stage renal disease (ESRD) patients stratified according to gender has not been previously investigated. In addition, we aimed to evaluate the diagnostic accuracy of the parameters to separate iron-deficiency anemia (IDA) from anemia of chronic disease. Materials and Methods. Iron status parameters and genetic analysis were performed in 126 ESRD patients and in 31 IDA patients as the control group. Results. ESRD patients had significantly higher ferritin and hepcidin-25 (<0.001) relative to IDA patients. Cut-off values with the best diagnostic accuracy were found for hepcidin ≥9.32 ng/mL, ferritin ≥48.2 μg/L, transferrin saturation ≥16.8%, and MCV ≥81 fL. Interaction between gender and HFE haplotypes for the hepcidin-25 and ferritin levels in ESRD patients (p = 0 005, partial eta squared = 0 09; p = 0 027, partial eta squared = 0 06, respectively) was found. Serum transferrin was influenced by the combined effect of gender and TMPRSS6 A736V polymorphism in ESRD patients (p = 0 002, partial eta squared = 0 07). Conclusion. Our findings could contribute to the further investigation of mechanisms involved in the pathophysiology and important gender-related involvement of the TMPRSS6 and HFE polymorphisms on anemia in ESRD patients. Copyright © 2019 Violeta Dopsaj et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background. Influence of TMPRSS6 A736V and HFE (C282Y and H63D) polymorphisms on serum hepcidin-25 levels and iron status parameters in end-stage renal disease (ESRD) patients stratified according to gender has not been previously investigated. In addition, we aimed to evaluate the diagnostic accuracy of the parameters to separate iron-deficiency anemia (IDA) from anemia of chronic disease. Materials and Methods. Iron status parameters and genetic analysis were performed in 126 ESRD patients and in 31 IDA patients as the control group. Results. ESRD patients had significantly higher ferritin and hepcidin-25 (<0.001) relative to IDA patients. Cut-off values with the best diagnostic accuracy were found for hepcidin ≥9.32 ng/mL, ferritin ≥48.2 μg/L, transferrin saturation ≥16.8%, and MCV ≥81 fL. Interaction between gender and HFE haplotypes for the hepcidin-25 and ferritin levels in ESRD patients (p = 0 005, partial eta squared = 0 09; p = 0 027, partial eta squared = 0 06, respectively) was found. Serum transferrin was influenced by the combined effect of gender and TMPRSS6 A736V polymorphism in ESRD patients (p = 0 002, partial eta squared = 0 07). Conclusion. Our findings could contribute to the further investigation of mechanisms involved in the pathophysiology and important gender-related involvement of the TMPRSS6 and HFE polymorphisms on anemia in ESRD patients. Copyright © 2019 Violeta Dopsaj et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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[No abstract available]

Introduction: Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive disorder with a progressive clinical course. In addition to symptomatic therapy, DBS has been increasingly recognized as a potential therapeutic strategy, especially in severe cases. Therefore, we wanted to report our experience regarding benefits of DBS in five PKAN cases in 3-year follow-up study. Methods: Five genetically confirmed PKAN patients from Serbia underwent GPi-DBS. To assess clinical outcome, we reviewed medical charts and applied: Schwab and England Activities of Daily Living Scale (S&E), EQ-5D questionnaire for quality of life, Patient Global Impression of Improvement (GPI-I), Functional Independence Measure (FIM), Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS), Barry Albright Dystonia Scale (BAD). Patients were evaluated in five visits: at the disease onset, 5 years after the onset, before surgery, 6 months and 14–36 months after the surgery. Improvement of 20% was accepted as significant. Results: Overall, dystonia significantly improved after GPi-DBS at 6 and 14–36 months postoperatively, when assessed by the BFMDRS and BAD. However, two patients failed to improve considerably. Four patients reported improvement on GPI-I, while one remained unchanged. Three patients reported significant improvement, when assessed with S&E and FIM. EQ-5D showed the most prominent improvement in the domains of mobility and pain/discomfort. Conclusion: Three out of our five patients experienced beneficial effects of the GPi-DBS, in up to 36 months follow-up. Two patients who had not reached significant improvement had longer disease duration; therefore, it might be reasonable to recommend GPi-DBS as soon as dystonia became disabling. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.

Introduction: Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive disorder with a progressive clinical course. In addition to symptomatic therapy, DBS has been increasingly recognized as a potential therapeutic strategy, especially in severe cases. Therefore, we wanted to report our experience regarding benefits of DBS in five PKAN cases in 3-year follow-up study. Methods: Five genetically confirmed PKAN patients from Serbia underwent GPi-DBS. To assess clinical outcome, we reviewed medical charts and applied: Schwab and England Activities of Daily Living Scale (S&E), EQ-5D questionnaire for quality of life, Patient Global Impression of Improvement (GPI-I), Functional Independence Measure (FIM), Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS), Barry Albright Dystonia Scale (BAD). Patients were evaluated in five visits: at the disease onset, 5 years after the onset, before surgery, 6 months and 14–36 months after the surgery. Improvement of 20% was accepted as significant. Results: Overall, dystonia significantly improved after GPi-DBS at 6 and 14–36 months postoperatively, when assessed by the BFMDRS and BAD. However, two patients failed to improve considerably. Four patients reported improvement on GPI-I, while one remained unchanged. Three patients reported significant improvement, when assessed with S&E and FIM. EQ-5D showed the most prominent improvement in the domains of mobility and pain/discomfort. Conclusion: Three out of our five patients experienced beneficial effects of the GPi-DBS, in up to 36 months follow-up. Two patients who had not reached significant improvement had longer disease duration; therefore, it might be reasonable to recommend GPi-DBS as soon as dystonia became disabling. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.

Pregnancies complicated with either pregestational or gestational diabetes mellitus deserve great attention due to their complexity and potential subsequent complications for both mother and the fetus. Based on already proven role of glycemic variability in the development of these, improving glucose monitoring continues to be an important step towards preventing adverse outcomes. Besides already well-established self-monitoring of glycemia, newer devices in the form of continuous glucose monitoring have found their place due to their proven preciseness and non-invasiveness. This paper has the aim to analyze results and conclusions of obtained, newer studies focused on these methods of glucose monitoring and to also give a closer insight of their usability and limitations. © 2024, Serbia Medical Society. All rights reserved.

Introduction: The impact of activated blood and endothelial cells on the thrombosis in myeloproliferative neoplasms (MPN) has not yet been clarified. We prospectively analyzed correlation between circulating leukocyte-platelet aggregates and soluble selectins to thrombosis occurrence in MPN, in the context of standard and cardiovascular risk factors, and different clinical and biological characteristics. Methods: Flow cytometric analysis of neutrophil-platelet (Neu-Plt) and monocyte-platelet (Mo-Plt) aggregates in peripheral blood, as well as quantification of soluble E-/L-/P-selectins by enzyme immunoassay, was performed on 95 newly diagnosed MPN patients. Results: During the follow-up, thrombosis occurred in 12.6% MPN patients (arterial 9.4%, venous 3.2%), with a mean time of 39 months. The overall incidence rate of main thrombotic events was 4.36 per 100 patient-years. The incidence of arterial hypertension (HTA) was significantly higher in patients with thrombosis, compared to those without thrombosis (P <.05). The level of soluble P-selectin was significantly higher in patients with thrombosis compared to those without thrombosis (346.89 ng/mL vs 286.39 ng/mL, P =.034). The mean level of Neu-Plt (26.7% vs 22.4%) and Mo-Plt (17.8% vs 12.3%) aggregates did not differ significantly between the groups with and without thrombosis. A multivariate COX proportional hazard regression model confirmed an independent predictive significance of Mo-Plt aggregates (HR = 1.561, 95% CI: 1.007-2.420, P =.046), as well as the cumulative effect of Mo-Plt aggregates and HTA (HR = 1.975, 95%CI: 1.215-3.212, P =.006) for thrombosis occurrence. Conclusion: Monocyte-platelet aggregates represent an independent risk factor for thrombosis occurrence, further on supported by HTA. © 2021 John Wiley & Sons Ltd

Introduction: The impact of activated blood and endothelial cells on the thrombosis in myeloproliferative neoplasms (MPN) has not yet been clarified. We prospectively analyzed correlation between circulating leukocyte-platelet aggregates and soluble selectins to thrombosis occurrence in MPN, in the context of standard and cardiovascular risk factors, and different clinical and biological characteristics. Methods: Flow cytometric analysis of neutrophil-platelet (Neu-Plt) and monocyte-platelet (Mo-Plt) aggregates in peripheral blood, as well as quantification of soluble E-/L-/P-selectins by enzyme immunoassay, was performed on 95 newly diagnosed MPN patients. Results: During the follow-up, thrombosis occurred in 12.6% MPN patients (arterial 9.4%, venous 3.2%), with a mean time of 39 months. The overall incidence rate of main thrombotic events was 4.36 per 100 patient-years. The incidence of arterial hypertension (HTA) was significantly higher in patients with thrombosis, compared to those without thrombosis (P <.05). The level of soluble P-selectin was significantly higher in patients with thrombosis compared to those without thrombosis (346.89 ng/mL vs 286.39 ng/mL, P =.034). The mean level of Neu-Plt (26.7% vs 22.4%) and Mo-Plt (17.8% vs 12.3%) aggregates did not differ significantly between the groups with and without thrombosis. A multivariate COX proportional hazard regression model confirmed an independent predictive significance of Mo-Plt aggregates (HR = 1.561, 95% CI: 1.007-2.420, P =.046), as well as the cumulative effect of Mo-Plt aggregates and HTA (HR = 1.975, 95%CI: 1.215-3.212, P =.006) for thrombosis occurrence. Conclusion: Monocyte-platelet aggregates represent an independent risk factor for thrombosis occurrence, further on supported by HTA. © 2021 John Wiley & Sons Ltd

Introduction: In this study we aimed to perform the first research on the current state of compulsory basic and clinical courses in genetics for medical students offered at medical faculties in six Balkan countries with Slavic languages (Bosnia and Herzegovina, Croatia, Montenegro, North Macedonia, Serbia, and Slovenia). Materials and Methods: The study was conducted from June to September 2021. One representative from each country was invited to collect and interpret the data for all medical faculties in their respective country. All representatives filled a questionnaire, which consisted of two sets of questions. The first set of questions was factual and contained specific questions about medical faculties and design of compulsory courses, whereas the second set of questions was more subjective and inquired the opinion of the representatives about mandatory education in clinical medical genetics in their countries and internationally. In addition, full course syllabi were analysed for course aims, learning outcomes, course content, methods for student evaluation and literature. Results: Detailed analysis was performed for a total of 22 medical faculties in Bosnia and Herzegovina (6), Croatia (4), Montenegro (1), North Macedonia (3), Serbia (6), and Slovenia (2). All but the two medical faculties in Slovenia offer either compulsory courses in basic education in human genetics (16 faculties/courses) or clinical education in medical genetics (3 faculties/courses). On the other hand, only the medical faculty in Montenegro offers both types of education, including one course in basic education in human genetics and one in clinical education in medical genetics. Most of the basic courses in human genetics have similar aims, learning outcomes and content. Conversely, clinical courses in medical genetics are similar concerning study year position, number of contact hours, ECTS (European Credit Transfer and Accumulation System) and contents, but vary considerably regarding aims, learning outcomes, ratio of types of classes, teaching methods and student evaluation. Conclusion: Our results emphasise the need for future collaboration in reaching a consensus on medical genetics education in Balkan countries with Slavic languages. Further research warrants the analysis of performance of basic courses, as well as introducing clinical courses in medical genetics to higher years of study across Balkan countries. Copyright © 2022 Pereza, Terzić, Plaseska-Karanfilska, Miljanović, Novaković, Poslon, Ostojić and Peterlin.

Introduction: In this study we aimed to perform the first research on the current state of compulsory basic and clinical courses in genetics for medical students offered at medical faculties in six Balkan countries with Slavic languages (Bosnia and Herzegovina, Croatia, Montenegro, North Macedonia, Serbia, and Slovenia). Materials and Methods: The study was conducted from June to September 2021. One representative from each country was invited to collect and interpret the data for all medical faculties in their respective country. All representatives filled a questionnaire, which consisted of two sets of questions. The first set of questions was factual and contained specific questions about medical faculties and design of compulsory courses, whereas the second set of questions was more subjective and inquired the opinion of the representatives about mandatory education in clinical medical genetics in their countries and internationally. In addition, full course syllabi were analysed for course aims, learning outcomes, course content, methods for student evaluation and literature. Results: Detailed analysis was performed for a total of 22 medical faculties in Bosnia and Herzegovina (6), Croatia (4), Montenegro (1), North Macedonia (3), Serbia (6), and Slovenia (2). All but the two medical faculties in Slovenia offer either compulsory courses in basic education in human genetics (16 faculties/courses) or clinical education in medical genetics (3 faculties/courses). On the other hand, only the medical faculty in Montenegro offers both types of education, including one course in basic education in human genetics and one in clinical education in medical genetics. Most of the basic courses in human genetics have similar aims, learning outcomes and content. Conversely, clinical courses in medical genetics are similar concerning study year position, number of contact hours, ECTS (European Credit Transfer and Accumulation System) and contents, but vary considerably regarding aims, learning outcomes, ratio of types of classes, teaching methods and student evaluation. Conclusion: Our results emphasise the need for future collaboration in reaching a consensus on medical genetics education in Balkan countries with Slavic languages. Further research warrants the analysis of performance of basic courses, as well as introducing clinical courses in medical genetics to higher years of study across Balkan countries. Copyright © 2022 Pereza, Terzić, Plaseska-Karanfilska, Miljanović, Novaković, Poslon, Ostojić and Peterlin.

Background: Mutations in GNAL (DYT25) have recently been established as the first confirmed cause of focal or segmental adult-onset dystonia. Mutation carriers show craniocervical involvement; however, the GNAL mutational and phenotypic spectrum remain to be further characterized, and guidelines for diagnostic testing need to be established. Methods: The authors used Sanger sequencing to test for changes in the GNAL coding or splice-site regions in 236 Serbian patients suffering from isolated dystonia with craniocervical involvement. Results: One novel likely pathogenic substitution (c.1061T>C; p.Val354Ala) in GNAL was detected in a sporadic cervical dystonia patient (mutation frequency: 0.4%). This mutation was not present in the DNA of either parent, despite confirmed parentage. Conclusions: This is the first report of a de novo GNAL mutation causing genetically proven, seemingly sporadic DYT25 dystonia. Our finding highlights the importance of genetic testing for GNAL mutations in establishing the molecular diagnosis even for patients with a negative family history. © 2014 International Parkinson and Movement Disorder Society.

Background: Mutations in GNAL (DYT25) have recently been established as the first confirmed cause of focal or segmental adult-onset dystonia. Mutation carriers show craniocervical involvement; however, the GNAL mutational and phenotypic spectrum remain to be further characterized, and guidelines for diagnostic testing need to be established. Methods: The authors used Sanger sequencing to test for changes in the GNAL coding or splice-site regions in 236 Serbian patients suffering from isolated dystonia with craniocervical involvement. Results: One novel likely pathogenic substitution (c.1061T>C; p.Val354Ala) in GNAL was detected in a sporadic cervical dystonia patient (mutation frequency: 0.4%). This mutation was not present in the DNA of either parent, despite confirmed parentage. Conclusions: This is the first report of a de novo GNAL mutation causing genetically proven, seemingly sporadic DYT25 dystonia. Our finding highlights the importance of genetic testing for GNAL mutations in establishing the molecular diagnosis even for patients with a negative family history. © 2014 International Parkinson and Movement Disorder Society.

In this study we report clinical and imaging data from a multigenerational Serbian family with idiopathic basal ganglia calcification (IBGC) and exclusion of linkage to chromosome 14q, 2q37 and 8p21.1-q11.23. Fourteen out of 18 family members were personally examined and 11 of them were scanned with computed tomography (CT). CT scans revealed existence of symmetrical calcifications in six family members from three generations (four symptomatic and two asymptomatic). Age at onset of clinical symptoms varied between 22.0 and 55.4 years. The main clinical findings included parkinsonism, severe gait disturbances with freezing of gait, and dyskinesia. Hyperechogenicities identified by transcranial sonography corresponded well to the CT images of hyperintense calcifications in the same structures, whereas brain perfusion single photon emission computed tomography demonstrated predominant hypoperfusion in the frontal cortex and the basal ganglia. After exclusion of linkage to known loci, our pedigree with IBGC further demonstrates locus heterogeneity in this disorder. Analysis of clinically affected individuals supports observation that the clinical features of IBGC appear to be varied both within and between families. The age at onset of the clinical symptoms appeared to be decreasing in two observed transmissions, suggestive of possible genetic anticipation. © 2011 Springer-Verlag.