{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:40:57Z","timestamp":1790642457221,"version":"4.1.0"},"reference-count":38,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,12,5]],"date-time":"2019-12-05T00:00:00Z","timestamp":1575504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Purpose: to determine a detailed clinical and haplotypic variability of the Slovenian USH2A patients with homozygous c.11864G&gt;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&gt;A mutation. Results: The c.11864G&gt;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) \u2264 0.05 at the average age of 66 years visual field diameter less than 20\u00b0 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.<\/jats:p>","DOI":"10.3390\/genes10121015","type":"journal-article","created":{"date-parts":[[2019,12,5]],"date-time":"2019-12-05T11:16:23Z","timestamp":1575544583000},"page":"1015","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Clinical and Haplotypic Variability of Slovenian USH2A Patients Homozygous for the c. 11864G&gt;A Nonsense Mutation"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3394-7690","authenticated-orcid":false,"given":"Andrej","family":"Zupan","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics, Institute of Pathology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6132-4808","authenticated-orcid":false,"given":"Ana","family":"Fakin","sequence":"additional","affiliation":[{"name":"Eye Hospital, University Medical Centre Ljubljana, Grablovi\u010deva 46, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saba","family":"Battelino","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia"},{"name":"Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Jarc-Vidmar","sequence":"additional","affiliation":[{"name":"Eye Hospital, University Medical Centre Ljubljana, Grablovi\u010deva 46, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6878-8904","authenticated-orcid":false,"given":"Marko","family":"Hawlina","sequence":"additional","affiliation":[{"name":"Eye Hospital, University Medical Centre Ljubljana, Grablovi\u010deva 46, 1000 Ljubljana, Slovenia"},{"name":"Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crystel","family":"Bonnet","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de G\u00e9n\u00e9tique et Physiologie de l\u2019Audition, Institut Pasteur, 75015 Paris, France"},{"name":"Unit\u00e9 Mixte de Recherche en Sant\u00e9 (UMRS) 1120, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), 75015 Paris, France"},{"name":"Complexit\u00e9 du Vivant, Sorbonne Universit\u00e9s, Universit\u00e9 Pierre et Marie Curie, Universit\u00e9 Paris 06, 75005 Paris, France"},{"name":"Institut de l\u2019Audition, 75012 Paris, France"},{"name":"Syndrome de Usher et Autres Atteintes R\u00e9tino-Cochl\u00e9aires, Institut de la Vision, 75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Petit","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de G\u00e9n\u00e9tique et Physiologie de l\u2019Audition, Institut Pasteur, 75015 Paris, France"},{"name":"Unit\u00e9 Mixte de Recherche en Sant\u00e9 (UMRS) 1120, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), 75015 Paris, France"},{"name":"Complexit\u00e9 du Vivant, Sorbonne Universit\u00e9s, Universit\u00e9 Pierre et Marie Curie, Universit\u00e9 Paris 06, 75005 Paris, France"},{"name":"Institut de l\u2019Audition, 75012 Paris, France"},{"name":"Syndrome de Usher et Autres Atteintes R\u00e9tino-Cochl\u00e9aires, Institut de la Vision, 75012 Paris, France"},{"name":"Coll\u00e8ge de France, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9912-3331","authenticated-orcid":false,"given":"Damjan","family":"Glava\u010d","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Institute of Pathology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.bbadis.2014.11.020","article-title":"Usher Syndrome: Hearing Loss, Retinal Degeneration and Associated Abnormalities","volume":"1852","author":"Mathur","year":"2015","journal-title":"Biochim. 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