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Abstract: Hereditary optic neuropathies comprise a genetically heterogeneous group of disorders caused by pathogenic variants in mitochondrial and nuclear genes. Despite increasing diagnostic yields, many patients remain without a molecular diagnosis. We report a novel candidate heterozygous variant in the PHB1 (Prohibitin 1) gene in a large family affected by autosomal dominant optic atrophy. A three-generation family with slowly progressive visual acuity loss due to optic neuropathy and an apparent auto-somal dominant pattern was clinically characterized and recruited for genetic counseling. Exome sequencing and genome-based linkage mapping were performed, alongside protein modeling and in vitro experiments to obtain functional evidence. Family-based whole-genome linkage mapping identified a heterozygous missense variant, c.440C>T (p.Ser147Phe), in PHB1 in all five affected individuals. The variant substitutes p.Ser147Phe within an evolutionarily conserved alpha-helix domain of PHB1, a mitochondrial protein with multiple roles. In silico modeling suggested that p.Ser147Phe may disrupt PHB1 stability and function through loss of hydrogen bonding, steric hindrance, and altered hydrophobic interactions. In vitro experiments suggested potential alterations in mitochondrial dynamics in variant carriers, including a changed ratio of L- OPA1 to S- OPA1 compared with non-carriers. We present initial evidence that PHB1 is a novel candidate gene potentially associated with dominant opticatrophy or a related mitochondrial disorder. This represents the first report implicating PHB1 in a Mendelian disease. Further studies are required to validate this association.
Keywords: PHB1, candidate genes, dominant optic atrophy, mitochondrial dysfunction
Published in DiRROS: 27.07.2026; Views: 126; Downloads: 89
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Abstract: Jan Šedivý ob koncu dvajsetih let 20. stoletja ni samo oral ledine s svojimi poglobljenimi predstavitvami beloruske in ukrajinske kulture, marveč se tudi njegov pristop razlikuje od tistega, ki je zlasti po drugi svetovni vojni v slovenskem prostoru prevladoval. To je bilo povezano z zgodovinskim trenutkom, v katerem so se Belorusi in Ukrajinci znašli v času zgodovinarjevega študija v Pragi. Poznejši razvoj je precej osramotil Šedivýjev optimizem s konca dvajsetih let. Skoraj popolno uničenje komaj oblikovane ukrajinske in beloruske kulturne elite v tridesetih letih 20. stoletja in druga svetovna vojna, ki je med drugim ustvarila novo politično mitologijo, sta skupaj s precej dvoumno združitvijo velike večine Ukrajincev in Belorusov pod sovjetsko egido na novo narisali kulturni zemljevid Vzhodne Evrope tudi za Slovence.
Keywords: Belorusija, Ukrajina, Jan Šedivý, belorusizacija, ukrajinizacija, belorusko-slovenski stiki, ukrajinsko-slovenski stiki
Published in DiRROS: 17.06.2026; Views: 186; Downloads: 180
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Abstract: Congenital heart disease (CHD) is the most commonly detected congenital anomaly and affects up to 1% of all live-born neonates. Current guidelines support the use of chromosomal microarray analysis (CMA) and next-generation sequencing (NGS) as diagnostic approaches to identify genetic causes. The aim of our study was to evaluate the diagnostic yield of CMA and NGS in a cohort of neonates with both isolated and syndromic CHD. The present study included 188 infants under 28 days of age with abnormal echocardiography findings hospitalized at the Department of Neonatology, UMC Ljubljana, between January 2014 and December 2023. Phenotypic data were obtained for each infant via retrospective medical chart review. We established the genetic diagnosis of 22 distinct syndromes in 17% (32/188) of neonates. The most frequent genetic diagnoses in diagnosed cases were 22q11.2 microdeletion and CHARGE syndromes, followed by Noonan syndrome and Williams syndrome. In addition, we detected variants of uncertain significance in 4.8% (9/188) of neonates. Timely genetic diagnosis is important for the detection of syndrome-related comorbidities, prognosis, reproductive genetic risks and, when appropriate, genetic testing of other family members.
Keywords: congenital heart disease, chromosomal microarray analysis, next-generation sequencing, diagnostic yield
Published in DiRROS: 12.06.2026; Views: 216; Downloads: 150
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Keywords: mesomelic dysplasia, horseshoe kidney, transcriptome, zebrafsh model
Published in DiRROS: 09.06.2026; Views: 179; Downloads: 172
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Abstract: Background: Congenital erythrocytosis (CE) is increasingly recognized as the cause of erythrocytosis in patients in whom polycythemia vera and secondary acquired causes have been excluded. The aim of our study was to determine possible genetic background in patients with idiopathic erythrocytosis. Methods: 40 patients with idiopathic erythrocytosis, referred to our institution in a 5-year period, were analyzed. We collected data on erythropoietin (Epo) levels, hemoglobin (Hgb), hematocrit (Hct), erythrocyte count, age, gender, past thrombotic events, concomitant diseases, and smoking status. CE was tested using next-generation sequencing (NGS), in the majority of patients also measurement of P50 and Hgb electrophoresis were performed. Patients with signs of iron overload were tested for genetic variants in the HFE gene. Results: The median patient age at analysis was 46.5 years (range 22–73), with 37 out of 40 being males (93 %). The median Hgb, Hct and red blood cells count were 180 g/L, 0.51, 5.985 x 1012/L in men and 171 g/L, 0.50 and 5.68 x 1012/L in women, respectively. Epo levels were decreased in three, increased in one patient and within the normal range in the rest (median 7.55 mIU/mL; range 2.90–19.50). Eight patients (20 %) smoked. 32 (80 %) were treated with low-dose aspirin, and 20 (50 %) underwent at least one phlebotomy. Thromboembolic events were recorded in 2 patients (5 %). P50 was measured in 20 out of 40 patients, and it was above 24 mm Hg (3.12 kPa) in all of them. Hemoglobin electrophoresis was performed in 73 % of patients, with no abnormal Hgb detected. Variants in the HFE gene were found in 8 out of 40 patients (20 %), but in only one patient the results were associated with an increased risk for hemochromatosis. Although no pathogenic variants for CE were detected by NGS, two variants of uncertain significance, namely EGLN1 (NM_022051.2):c.1072C>T (p.(Pro358Ser)) and EGLN1 (NM_022051.2):c.1124A>G (p.(Glu375Gly)) were identified as strong etiologic candidates. Conclusion: CE is an extremely rare condition. Genetic testing is advised in young individuals with a long-standing persistent erythrocytosis, possibly with a family history and after exclusion of more frequent secondary causes and polycytemia vera.
Keywords: non-clonal erythrocytosis, congenital erythrocytosis, next-generation sequencing, erythropoietin, hemochromatosis
Published in DiRROS: 08.06.2026; Views: 187; Downloads: 149
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