1. Atypical Leber Hereditary Optic Neuropathy (LHON) associated with a novel MT-CYB:m.15309T>C(Ile188Thr) variantSanja Petrović Pajić, Ana Fakin, Martina Jarc-Vidmar, Maja Šuštar Habjan, Lucija Malinar, Kasja Pavlovic, Nina Krako Jakovljevic, Marija Volk, Aleš Maver, Gregor Jezernik, Damjan Glavač, Borut Peterlin, Marko Hawlina, 2025, izvirni znanstveni članek Povzetek: Background: The study presents a detailed examination and follow-up of a Slovenian patient with an Leber Hereditary Optic Neuropathy (LHON)-like phenotype and bilateral optic neuropathy in whom genetic analysis identified a novel variant MT-CYB:m.15309T>C (Ile188Thr). Methods: We provide detailed analysis of the clinical examinations of a male patient with bilateral optic neuropathy from the acute stage to 8 years of follow-up. Complete ophthalmological exam, electrophysiology and optical coherence tomography (OCT) segmentation were performed. The genotype analysis was performed with a complete screening of the mitochondrial genome. Furthermore, proteomic analysis of the protein structure and function was performed to assess the pathogenicity of a novel variant of unknown significance. Mitochondrial function analysis of the patient’s peripheral blood mononuclear cells (PBMCs) was performed with the objective of evaluating the mutation effect on mitochondrial function using flow cytometry and high-resolution respirometry. Results: The patient had a profound consecutive bilateral visual loss at 19 years of age due to optic neuropathy with characteristics of LHON; however, unlike patients with typical LHON, the patient experienced a fluctuation in visual function and significant late recovery. He had a total of three visual acuity deteriorations and improvements in the left eye, with concomitant visual loss in the right eye and a final visual acuity drop reaching nadir 9 months after onset. The visual loss was characterized by centrocecal scotoma, abnormal color vision and abnormal VEP, while deterioration of PERG N95 followed with a lag of several months. The OCT examination showed retinal nerve fiber layer thinning matching disease progression. Following a two-year period of legal blindness, the patient’s visual function started to improve, and over the course of 5 years, it reached 0.5 and 0.7 Snellen (0.3 and 0.15 LogMAR) visual acuity (VA). Mitochondrial sequencing identified a presumably pathogenic variant m.15309T>C in the MT-CYB gene at 65% heteroplasmy, belonging to haplogroup K. Mitochondrial function assessment of the patient’s PBMCs showed a lower respiration rate, an increase in reactive oxygen species production and the presence of mitochondrial depolarization, compared to an age- and sex-matched healthy control’s PBMCs. Conclusions: A novel variant in the MT-CYB:m.15309T>C (Ile188Thr) gene was identified in a patient with optic nerve damage and the LHON phenotype without any additional systemic features and atypical presentation of the disease with late onset of visual function recovery. The pathogenicity of the variant is supported by proteomic analysis and the mitochondrial dysfunction observed in the patient’s PBMCs.
Ključne besede: LHON, gene, electrophysiology, retinal segmentation, VA improvement, mitochondrial disfunction, proteomic analysis
Objavljeno v DiRROS: 10.11.2025; Ogledov: 56; Prenosov: 9
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2. Twenty-one days of bed rest alter motor unit properties and neuromuscular junction transmission in young adultsFabio Sarto, Miloš Kalc, Evgeniia Motanova, Martino V. Franchi, Daniel W Stashuk, Nina Murks, Giacomo Valli, Samuele Negro, Tomaž Prašnikar, Mladen Gasparini, Giovanni Martino, Giuseppe De Vito, Aleš Holobar, Boštjan Šimunič, Rado Pišot, Marco Vincenzo Narici, 2025, izvirni znanstveni članek Povzetek: Previous studies showed that properties of higher‐threshold motor units (MUs) and neuromuscular junction (NMJ) function are preserved during short‐term disuse. This study aimed to test how a longer disuse period affects MU properties, NMJ transmission, and NMJ morphology remodeling. Nine young healthy males (age: 18‐29 years) underwent 21 days of horizontal bed rest. Pre‐ (BR0) and post‐bed rest (BR21), quadriceps maximal voluntary contraction (MVC), and size were assessed. We combined intramuscular electromyography (iEMG) and high‐density surface electromyography (HDsEMG) recordings on the vastus lateralis to assess MU properties at 25% and 50% of MVC. Muscle biopsies and blood samples were also collected. Quadriceps MVC and size decreased at BR21. We found alterations in MU properties at both contraction intensities, including reduced discharge rate, MU potential area changes, and increased complexity. NMJ transmission was found to be reduced at BR21 at 25% MVC. This functional NMJ impairment was biochemically corroborated by an increase in serum C‐terminal agrin fragment concentration, a biomarker of NMJ instability. In addition, a direct assessment of NMJ morphology revealed the presence of some denervated NMJs exclusively at BR21. In conclusion, 21‐day bed rest altered MU properties across different contraction intensities and impaired NMJ transmission with initial signs of remodeling/denervation. Disuse duration appears to be a critical factor, as previous shorter studies failed to detect some of these changes. We believe these findings are clinically relevant for disuse after trauma, surgery, or illness, and may support the development of effective countermeasures.
Ključne besede: disuse, unloading, physical inactivity, electrophysiology, electromyography
Objavljeno v DiRROS: 13.05.2025; Ogledov: 590; Prenosov: 256
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