المؤلفون: Kiraly, Peter, Seitz, Immanuel P., Abdalla Elsayed, Maram E. A., Downes, Susan M., Patel, Chetan K., Charbel Issa, Peter, Birtel, Johannes, Mautone, Luca, Dulz, Simon, Atiskova, Yevgeniya, Herrmann, Philipp, Vrabič, Nika, Jarc-Vidmar, Martina, Hawlina, Marko, Fischer, M. Dominik

المصدر: Frontiers in Medicine ; volume 10 ; ISSN 2296-858X

مصطلحات موضوعية: General Medicine

الوصف: Introduction X-linked retinoschisis (XLRS) is a potential target for gene supplementation approaches. To establish potential structural and functional endpoints for clinical trials, a comprehensive understanding of the inter-eye symmetry, relationship between structural and functional parameters, and disease progression is vital. Methods In this retrospective multicentre study, 118 eyes of 59 XLRS patients with RS1 mutations were assessed. Information from center databases included: RS1 variant; age at presentation; best-corrected visual acuity (BCVA), central retinal thickness (CRT), macular volume (MV) at presentation and at the last follow up; full-field electroretinogram (ERG) findings; presence of peripheral retinoschisis and complications (vitreous hemorrhage, retinal detachment); treatment with systemic or topical carbonic anhydrase inhibitors (CAI). Results Inter-eye symmetry revealed strong correlation in CRT ( r = 0.77; p < 0.0001) and moderate correlations in MV ( r = 0.51, p < 0.0001) and BCVA ( r = 0.49; p < 0.0001). Weak or no correlations were observed between BCVA and structural parameters (CRT, MV). Peripheral retinoschisis was observed in 40 (68%), retinal detachment in 9 (15%), and vitreous hemorrhage in 5 (8%) patients, respectively. Longitudinal examinations (mean, 4.3 years) showed no BCVA changes; however, a reduction of the CRT ( p = 0.02), and MV ( p = 0.01) was observed. Oral and/or topical CAI treatment did not significantly alter the CRT ( p = 0.34). Discussion The XLRS phenotype demonstrates a strong CRT symmetry between the eyes within individual patients and stable BCVA over several years. BCVA exhibits a weak correlation with the morphological parameters of retinal thickness (CRT MV). In our cohort, longitudinal functional changes were not significant, likely attributed to the short average follow-up period. Furthermore, CAI treatment didn’t influence both morphological and functional outcomes.

الإتاحة: https://doi.org/10.3389/fmed.2023.1331889Test

المؤلفون: Lumi, Xhevat, Confalonieri, Filippo, Ravnik-Glavač, Metka, Goričar, Katja, Blagus, Tanja, Dolžan, Vita, Petrovski, Goran, Hawlina, Marko, Glavač, Damjan

المصدر: 2073-4425.

الوصف: This study investigated the association between certain genetic variations and the risk of developing proliferative vitreoretinopathy (PVR) after surgery. The study was conducted on 192 patients with primary rhegmatogenous retinal detachment (RRD) who underwent 3-port pars plana vitrectomy (PPV). The distribution of single nucleotide polymorphisms (SNPs) located in genes involved in inflammation and oxidative stress associated with PVR pathways were analyzed among patients with and without postoperative PVR grade C1 or higher. A total of 7 defined SNPs of 5 genes were selected for genotyping: rs4880 (SOD2); rs1001179 (CAT); rs1050450 (GPX1); rs1143623, rs16944, rs1071676 (IL1B); rs2910164 (MIR146A) using competitive allele-specific polymerase chain reaction. The association of SNPs with PVR risk was evaluated using logistic regression. Furthermore, the possible association of SNPs with postoperative clinical parameters was evaluated using non-parametric tests. The difference between two genotype frequencies between patients with or without PVR grade C1 or higher was found to be statistically significant: SOD2 rs4880 and IL1B rs1071676. Carriers of at least one polymorphic IL1B rs1071676 GG allele appeared to have better postoperative best-corrected visual acuity only in patients without PVR (p = 0.070). Our study suggests that certain genetic variations may play a role in the development of PVR after surgery. These findings may have important implications for identifying patients at higher risk for PVR and developing new treatments.

العلاقة: Lumi, Xhevat Confalonieri, Filippo Ravnik-Glavač, Metka Goričar, Katja Blagus, Tanja Dolžan, Vita Petrovski, Goran Hawlina, Marko Glavač, Damjan . Inflammation and Oxidative Stress Gene Variability in Retinal Detachment Patients with and without Proliferative Vitreoretinopathy. Genes. 2023, 14(4); http://hdl.handle.net/10852/107000Test; 2160401; info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Genes&rft.volume=14&rft.spage=&rft.date=2023; Genes; 14; https://doi.org/10.3390/genes14040804Test

الإتاحة: https://doi.org/10.3390/genes14040804Test
http://hdl.handle.net/10852/107000Test

المؤلفون: Barboni, Mirella T. S., Sustar Habjan, Maja, Petrovic Pajic, Sanja, Hawlina, Marko

المصدر: Documenta Ophthalmologica; Jun2024, Vol. 148 Issue 3, p133-143, 11p

مستخلص: Purpose: Leber hereditary optic neuropathy (LHON) affects retinal ganglion cells causing severe vision loss. Pattern electroretinogram and photopic negative response (PhNR) of the light-adapted (LA) full-field electroretinogram (ERG) are typically affected in LHON. In the present study, we evaluated dark-adapted (DA) and LA oscillatory potentials (OPs) of the flash ERG in genetically characterized LHON patients to dissociate slow from fast components of the response. Methods: Seven adult patients (mean age = 28.4 ± 5.6) in whom genetic diagnosis confirmed LHON with mtDNA or nuclear DNAJC30 (arLHON) pathogenic variants were compared to 12 healthy volunteers (mean age = 35.0 ± 12.1). Full-field ERGs were recorded from both eyes. Offline digital filters at 50, 75 and 100 Hz low cutoff frequencies were applied to isolate high-frequency components from the original ERG signals. Results: ERG a-waves and b-waves were comparable between LHON patients and controls, while PhNR was significantly reduced (p = 0.009) in LHON patients compared to controls, as expected. OPs derived from DA signals (75 Hz low cutoff frequency) showed reduced peak amplitude for OP2 (p = 0.019). LA OP differences between LHON and controls became significant (OP2: p = 0.047, OP3: p = 0.039 and OP4: p = 0.013) when the 100 Hz low-cutoff frequency filter was applied. Conclusions: Reduced OPs in LHON patients may represent disturbed neuronal interactions in the inner retina with preserved photoreceptoral (a-wave) to bipolar cell (b-wave) activation. Reduced DA OP2 and high-cutoff LA OP alterations may be further explored as functional measures to characterize LHON status and progression. [ABSTRACT FROM AUTHOR]

: Copyright of Documenta Ophthalmologica is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Andjelic, Sofija, Kreuzer, Martin, Hawlina, Marko

المصدر: Acta Ophthalmologica ; volume 102, issue S279 ; ISSN 1755-375X 1755-3768

الوصف: Aims/Purpose: To compare the bio‐macromolecular composition and the differences between the human cultured and post‐operative lens epithelial cells (LECs) on lens capsules (LCs) for a better understanding of posterior capsular opacification (PCO)—the most common complication of cataract surgery, and lens regeneration. Methods: The explants of the anterior portion of the LC containing the LECs, obtained from cataract surgery and cultivated under adherent conditions, as well as the post‐operative LC with LECs, were analysed by using synchrotron radiation‐based Fourier transform infrared (SR‐FTIR) microspectroscopy, a vibrational spectroscopic technique that allows monitoring of the entire biochemical status of the biological processes. The SR‐FTIR microspectroscopy setup installed on the beamline MIRAS at the Spanish synchrotron light source ALBA was used, where measurements were set to achieve single‐cell resolution, with high spectral stability and high photon flux. Results: We found that the differences exist between the composites of cultured and post‐operative LECs on LCs on the level of all chemical constituents: proteins, lipids, nucleic acids and carbohydrates as well as oxidative stress. The strongest differences are found in protein secondary structure contribution where the composite of primary LECs cultures on LC have more α‐helix (1652 cm −1 ) and post‐operative LC have more β‐sheet (1624 cm −1 and 1697 cm −1 ) secondary structures. The oxidative stress is more expressed in the composite of primary LECs cultures on LC and relatively less in the composite of post‐operative lens epithelium LECs on LC. Conclusions: Our results obtained by SR‐FTIR increase the knowledge about the total proteins, lipids, and nucleic acids in human primary cultures LECs while offering also evidence that SR‐FTIR is sensitive to the pathologic processes of LECs transdifferentiation. We showed that the composite of primary cultures LECs on LC have a distinct bio‐macromolecular composition compared to the composite of ...

الإتاحة: https://doi.org/10.1111/aos.15974Test

المؤلفون: Petzold, Axel, Fraser, Clare L, Abegg, Mathias, Alroughani, Raed, Alshowaeir, Daniah, Alvarenga, Regina, Andris, Cécile, Asgari, Nasrin, Barnett, Yael, Battistella, Roberto, Behbehani, Raed, Berger, Thomas, Bikbov, Mukharram M, Biotti, Damien, Biousse, Valerie, Boschi, Antonella, Brazdil, Milan, Brezhnev, Andrei, Calabresi, Peter A, Cordonnier, Monique, Costello, Fiona, Cruz, Franz M, Cunha, Leonardo Provetti, Daoudi, Smail, Deschamps, Romain, de Seze, Jerome, Diem, Ricarda, Etemadifar, Masoud, Flores-Rivera, Jose, Fonseca, Pedro, Frederiksen, Jette, Frohman, Elliot, Frohman, Teresa, Tilikete, Caroline Froment, Fujihara, Kazuo, Gálvez, Alberto, Gouider, Riadh, Gracia, Fernando, Grigoriadis, Nikolaos, Guajardo, José M, Habek, Mario, Hawlina, Marko, Martínez-Lapiscina, Elena H, Hooker, Juzar, Hor, Jyh Yung, Howlett, William, Huang-Link, Yumin, Idrissova, Zhannat, Illes, Zsolt, Jancic, Jasna, Jindahra, Panitha, Karussis, Dimitrios, Kerty, Emilia, Kim, Ho Jin, Lagrèze, Wolf, Leocani, Letizia, Levin, Netta, Liskova, Petra, Liu, Yaou, Maiga, Youssoufa, Marignier, Romain, McGuigan, Chris, Meira, Dália, Merle, Harold, Monteiro, Mário L R, Moodley, Anand, Moura, Frederico, Muñoz, Silvia, Mustafa, Sharik, Nakashima, Ichiro, Noval, Susana, Oehninger, Carlos, Ogun, Olufunmilola, Omoti, Afekhide, Pandit, Lekha, Paul, Friedemann, Rebolleda, Gema, Reddel, Stephen, Rejdak, Konrad, Rejdak, Robert, Rodriguez-Morales, Alfonso J, Rougier, Marie-Bénédicte, Sa, Maria Jose, Sanchez-Dalmau, Bernardo, Saylor, Deanna, Shatriah, Ismail, Siva, Aksel, Stiebel-Kalish, Hadas, Szatmary, Gabriella, Ta, Linh, Tenembaum, Silvia, Tran, Huy, Trufanov, Yevgen, Van Pesch, Vincent, Wang, An-Guor, Wattjes, Mike P, Willoughby, Ernest, Zakaria, Magd, Zvornicanin, Jasmin, Balcer, Laura, Plant, Gordon T

المساهمون: UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Service d'ophtalmologie, UCL - (SLuc) Service de neurologie

المصدر: The Lancet. Neurology, Vol. 21, no. 12, p. 1120-1134 (2022)

مصطلحات موضوعية: Humans, Retrospective Studies, Optic Neuritis, Neuromyelitis Optica, Multiple Sclerosis, Autoantibodies, Aquaporin 4

الوصف: There is no consensus regarding the classification of optic neuritis, and precise diagnostic criteria are not available. This reality means that the diagnosis of disorders that have optic neuritis as the first manifestation can be challenging. Accurate diagnosis of optic neuritis at presentation can facilitate the timely treatment of individuals with multiple sclerosis, neuromyelitis optica spectrum disorder, or myelin oligodendrocyte glycoprotein antibody-associated disease. Epidemiological data show that, cumulatively, optic neuritis is most frequently caused by many conditions other than multiple sclerosis. Worldwide, the cause and management of optic neuritis varies with geographical location, treatment availability, and ethnic background. We have developed diagnostic criteria for optic neuritis and a classification of optic neuritis subgroups. Our diagnostic criteria are based on clinical features that permit a diagnosis of possible optic neuritis; further paraclinical tests, utilising brain, orbital, and retinal imaging, together with antibody and other protein biomarker data, can lead to a diagnosis of definite optic neuritis. Paraclinical tests can also be applied retrospectively on stored samples and historical brain or retinal scans, which will be useful for future validation studies. Our criteria have the potential to reduce the risk of misdiagnosis, provide information on optic neuritis disease course that can guide future treatment trial design, and enable physicians to judge the likelihood of a need for long-term pharmacological management, which might differ according to optic neuritis subgroups.

العلاقة: boreal:276419; http://hdl.handle.net/2078.1/276419Test; info:pmid/36179757; urn:ISSN:1474-4422; urn:EISSN:1474-4465

الإتاحة: https://doi.org/10.1016/S1474-4422Test(22)00200-9
http://hdl.handle.net/2078.1/276419Test

المؤلفون: Petrovic Pajic, Sanja, Jarc-Vidmar, Martina, Fakin, Ana, Sustar Habjan, Maja, Brecelj, Jelka, Volk, Marija, Maver, Ales, Peterlin, Borut, Hawlina, Marko

المساهمون: Javna Agencija za Raziskovalno Dejavnost RS

المصدر: Frontiers in Neurology ; volume 13 ; ISSN 1664-2295

مصطلحات موضوعية: Neurology (clinical), Neurology

الوصف: Background We present the disease course and long-term follow-up of two patients who were phenotypically diagnosed with atypical Leber Hereditary Optic Neuropathy (LHON) 14 and 12 years ago, respectively, whereby whole exome sequencing revealed recently described recessive DNAJC30:c.152G>A 152 A>G (p.Tyr51Cys) homozygous pathogenic variant with significant spontaneous visual acuity recovery in one. Case presentation Two presented unrelated males with atypical LHON with sequential visual acuity (VA) loss were followed for many years. Both patients had negative family history. At the presentation at ages 17 (Case 1) and 18 years (Case 2), both had reduced visual acuity (Snellen): (Case 1) right eye (RE):CF 3m, left eye (LE):0.6, (Case 2) RE:0.2, LE:0.15; and color vision (Ishihara): (Case 1) 1/15 and 13/15; (Case 2) 2/15 and 3/15. Both had hyperemic optic disks (PNO) and central scotoma in their visual fields. Electrophysiology in the acute phase showed reduced and delayed visually evoked potentials (VEP) P100 in both patients, with reduced N95 amplitude in Case 2, and initially normal N95 amplitude in Case 1. Fluorescein angiography showed no early leakage with some late pooling at optic disks. Extensive clinical workout, including brain magnetic resonance imaging (MRI), aquaporin 4 (Aq4), and anti-myelin oligodendrocyte protein (anti-MOG) antibodies, was negative. Intravenous corticosteroids did not improve vision. Both experienced further deterioration several months after the onset accompanied by thinning of the peripapillary retinal nerve fiber layer (RNFL). Genetic testing for typical LHON pathogenic variants and whole mitochondrial DNA (mtDNA) sequencing was negative. 1 year after the onset, modest VA improvement began in Case 2 and continued over the next 3 years. VA improved bilaterally to 0.7, color vision 15/15, and islands of vision appeared within the visual field scotoma. VEP P100 peak time shortened, and amplitude increased, despite further RNFL thinning on optical coherent tomography ...

الإتاحة: https://doi.org/10.3389/fneur.2022.1003046Test

المؤلفون: Kobal, Nina, Hawlina, Marko

المصدر: Frontiers in Human Neuroscience ; volume 16 ; ISSN 1662-5161

مصطلحات موضوعية: Behavioral Neuroscience, Biological Psychiatry, Psychiatry and Mental health, Neurology, Neuropsychology and Physiological Psychology

الوصف: We reviewed the current state of knowledge regarding visual function and its suitability as part of medical examinations for driving licenses. We focused only on Group 1 drivers. According to previous studies, visual acuity, which is the most common test, is weakly associated with a higher risk of road accidents, with a greater role of visual field. The inclusion of the visual field test in medical examinations is therefore important, but the actual limit value is still unclear and further research in specific situations is needed. Color vision impairment was not found a threat to traffic safety. Contrast sensitivity decreases with age and is affected by abnormal eye conditions. Resulting glare can lead to an increased risk of traffic accidents during night driving in the elderly and others with conditions that impair contrast sensitivity. However, the universal cut-off limits have not been established either. The current European Union (EU) regulations therefore reflect minimum common denominator across the member states which may not entirely translate to optimal driving safety. Due to these open questions, standardized testing in simulators or on polygons that simulate real life conditions would be needed to better determine safe limits of visual function in different conditions. As there is a need to have better standardization across Europe regarding the requirements and rules regarding driving licenses in European countries, we first analyzed existing rules and compared them with each other, also in terms of deviations from the EU directive itself. We reviewed the literature in this field and prepared proposals for a more optimal regulation of the rules in the future. Particular attention is paid to the new method of examining the visual field that was created to respect the European directive. The paper can serve as a basis of information for research teams to design further protocols, as it gathers research findings to date on the importance and impact of various visual functions on driving safety, as ...

الإتاحة: https://doi.org/10.3389/fnhum.2022.927712Test

المؤلفون: Fakin, Ana, Bonnet, Crystel, Kurtenbach, Anne, Mohand-Said, Saddek, Zobor, Ditta, Stingl, Katarina, Testa, Francesco, Simonelli, Francesca, Sahel, José-Alain, Audo, Isabelle, Zrenner, Eberhart, Hawlina, Marko, Petit, Christine

المساهمون: University Medical Centre Ljubljana Ljubljana, Slovenia (UMCL), Institut de l'Audition Paris (IDA), Institut Pasteur Paris (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Eberhard Karls Universität Tübingen = University of Tübingen, Institut de la Vision, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO), Sorbonne Université (SU), Università degli studi della Campania "Luigi Vanvitelli" = University of the Study of Campania Luigi Vanvitelli, Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild AP-HP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Collège de France (CdF (institution)), This work was supported by the European Union Seventh Framework Programme under the grant agreement HEALTH-F2-2010-242013 (TREATRUSH), the Slovenian Research Agency (grant ARRS J3-1750), and the Tistou and Charlotte Kerstan Foundation, Tübingen., European Project: 242013,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,TREATRUSH(2010)

المصدر: ISSN: 1661-6596.

مصطلحات موضوعية: Usher syndrome (USH), USH2A, ADGRV1, VLGR1, GPR98, MASS1, retinitis pigmentosa, fundus autofluorescence, hyperautofluorescent ring, adhesion G protein-coupled receptor V1, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology

الوصف: International audience ; In contrast to USH2A, variants in ADGRV1 are a minor cause of Usher syndrome type 2, and the associated phenotype is less known. The purpose of the study was to characterize the retinal phenotype of 18 ADGRV1 patients (9 male, 9 female; median age 52 years) and compare it with that of 204 USH2A patients (111 male, 93 female; median age 43 years) in terms of nyctalopia onset, best corrected visual acuity (BCVA), fundus autofluorescence (FAF), and optical coherence tomography (OCT) features. There was no statistical difference in the median age at onset (30 and 18 years; Mann–Whitney U test, p = 0.13); the mean age when 50% of the patients reached legal blindness (≥1.0 log MAR) based on visual acuity (64 years for both groups; log-rank, p = 0.3); the risk of developing advanced retinal degeneration (patch or atrophy) with age (multiple logistic regression, p = 0.8); or the frequency of cystoid macular edema (31% vs. 26%, Fisher’s exact test, p = 0.4). ADGRV1 and USH2A retinopathy were indistinguishable in all major functional and structural characteristics, suggesting that the loss of function of the corresponding proteins produces similar effects in the retina. The results are important for counseling ADGRV1 patients, who represent the minor patient subgroup.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/34638692; info:eu-repo/grantAgreement/EC/FP7/242013/EU/Fighting blindness of Usher syndrome: diagnosis, pathogenesis and retinal treatment (TreatRetUsher)/TREATRUSH; hal-03417248; https://hal.sorbonne-universite.fr/hal-03417248Test; https://hal.sorbonne-universite.fr/hal-03417248/documentTest; https://hal.sorbonne-universite.fr/hal-03417248/file/ijms-22-10352.pdfTest; PUBMED: 34638692; PUBMEDCENTRAL: PMC8509029

الإتاحة: https://doi.org/10.3390/ijms221910352Test
https://hal.sorbonne-universite.fr/hal-03417248Test
https://hal.sorbonne-universite.fr/hal-03417248/documentTest
https://hal.sorbonne-universite.fr/hal-03417248/file/ijms-22-10352.pdfTest

المؤلفون: Fakin, Ana, Šuštar, Maja, Brecelj, Jelka, Bonnet, Crystel, Petit, Christine, Zupan, Andrej, Glavač, Damjan, Jarc-Vidmar, Martina, Battelino, Saba, Hawlina, Marko

المصدر: Genes, vol. 10, no. 12, art 956, 2019. ; ISSN: 2073-4425

مصطلحات موضوعية: USH2A-retinopathy, double hyperautofluorescent rings, electrophysiology, USH2A, usher syndrome, retinitis pigmentosa, fundus autofluorescence, cone-rod dystrophy, USH2A-retinopatija, dvojni hipevtrofluorescenčni obroči, elektrofiziologija, info:eu-repo/classification/udc/617.7

الوصف: USH2A mutation is the most common cause of retinitis pigmentosa, with or without hearing impairment. Patients most commonly exhibit hyperautofluorescent ring on fundus autofluorescence imaging (FAF) and rod-cone dystrophy on electrophysiology. A detailed study of three USH2A patients with a rare pattern of double hyperautofluorescent rings was performed. Twenty-four patients with typical single hyperautofluorescent rings were used for comparison of the ages of onset, visual fields, optical coherence tomography, electrophysiology, and audiograms. Double rings delineated the area of pericentral retinal degeneration in all cases. Two patients exhibited rod-cone dystrophy, whereas the third had a cone-rod dystrophy type of dysfunction on electrophysiology. There was minimal progression on follow-up in all three. Patients with double rings had significantly better visual acuity, cone function, and auditory performance than the single ring group. Double rings were associated with combinations of null and missense mutations, none of the latter found in the single ring patients. According to these findings, the double hyperautofluorescent rings indicate a mild subtype of USH2A disease, characterized by pericentral retinal degeneration, mild to moderate hearing loss, and either a rod-cone or cone-rod pattern on electrophysiology, the latter expanding the known clinical spectrum of USH2A-retinopathy.

وصف الملف: application/pdf; text/url

العلاقة: info:eu-repo/grantAgreement/ARRS//P3-0333; info:eu-repo/grantAgreement/EC/FP7/242013; https://repozitorij.uni-lj.si/IzpisGradiva.php?id=133108Test; https://repozitorij.uni-lj.si/Dokument.php?id=150910&dnTest=; https://repozitorij.uni-lj.si/Dokument.php?id=150909&dnTest=; https://plus.si.cobiss.net/opac7/bib/34598361?lang=slTest

الإتاحة: https://doi.org/10.3390/genes10120956Test
https://repozitorij.uni-lj.si/IzpisGradiva.php?id=133108Test
https://repozitorij.uni-lj.si/Dokument.php?id=150910&dnTest=
https://repozitorij.uni-lj.si/Dokument.php?id=150909&dnTest=
https://plus.si.cobiss.net/opac7/bib/34598361?lang=slTest

المؤلفون: Zupan, Andrej, Fakin, Ana, Battelino, Saba, Jarc-Vidmar, Martina, Hawlina, Marko, Bonnet, Crystel, Petit, Christine, Glavač, Damjan

المصدر: Genes, vol. 10, no. 12, art 1015, 2019. ; ISSN: 2073-4425

مصطلحات موضوعية: USH2A, haplotypic variability, homozygous mutation, usher syndrome, founder effect, haplotype analysis, high resolution melting analysis, haplotipska spremenljivost, homozigotna mutacija, info:eu-repo/classification/udc/617.7

الوصف: Purpose: to determine a detailed clinical and haplotypic variability of the Slovenian USH2A patients with homozygous c.11864G>A (p.Trp3955Ter) nonsense mutation and to develop sensitive, accurate and rapid screening test. Methods: Ten unrelated homozygous patients with detailed ophthalmological exam were included in our study. The High-Resolution Melting (HRM) method was developed for fast and reliable detection of the c.11864G>A mutation. Results: The c.11864G>A mutation represents the vast majority of pathogenic alleles in Slovenian USH2A-Usher syndrome population (84%). The median age of onset of nyctalopia was 16 years and all patients younger than 40 years had hyperautofluorescent rings on fundus autofluorescence imaging. The Kaplan Meier survival analysis showed a decline of central vision after the age of 40, with 50% patients reaching visual acuity (VA) ≤ 0.05 at the average age of 66 years visual field diameter less than 20° at the average age of 59 years. There was a relatively large phenotypic variability in the retinal and audiological phenotype. Analysis of the p.Trp3955Ter-homozygous patients revealed four different haplotypes, with the frequency of the most common haplotype ~65%. Disease severity did not correlate with the haplotype. Conclusions: According to the natural history of homozygous p.Trp3955Ter patients any therapy aimed to slow disease progression in these patients would be best started before the age of 40. Phenotypic variability suggests the presence of cis and/or trans factors outside the USH2A gene that are able to affect disease severity. High frequency of p.Trp3955Ter mutation in Slovenian USH2A gene pool appears to be initiated from different unrelated founders because of migrations from neighboring populations. The mutation on haplotype 2 seems to be the major founder allele.

وصف الملف: application/pdf; text/url

العلاقة: info:eu-repo/grantAgreement/ARRS//P3-0054; info:eu-repo/grantAgreement/ARRS//P3-0333; https://repozitorij.uni-lj.si/IzpisGradiva.php?id=133089Test; https://repozitorij.uni-lj.si/Dokument.php?id=150878&dnTest=; https://repozitorij.uni-lj.si/Dokument.php?id=150877&dnTest=; https://plus.si.cobiss.net/opac7/bib/34616281?lang=slTest

الإتاحة: https://doi.org/10.3390/genes10121015Test
https://repozitorij.uni-lj.si/IzpisGradiva.php?id=133089Test
https://repozitorij.uni-lj.si/Dokument.php?id=150878&dnTest=
https://repozitorij.uni-lj.si/Dokument.php?id=150877&dnTest=
https://plus.si.cobiss.net/opac7/bib/34616281?lang=slTest