{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T10:32:35Z","timestamp":1774953155221,"version":"3.50.1"},"reference-count":71,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T00:00:00Z","timestamp":1675123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft","award":["418081722"],"award-info":[{"award-number":["418081722"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["433158657"],"award-info":[{"award-number":["433158657"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["Metalli pesanti e degenerazioni retiniche: geni o ambiente?"],"award-info":[{"award-number":["Metalli pesanti e degenerazioni retiniche: geni o ambiente?"]}]},{"name":"Fondo Sociale Europeo REACT EU\u2014Programma Operativo Nazionale \u201cRicerca e innovazione\u201d 2014\u20132020","award":["418081722"],"award-info":[{"award-number":["418081722"]}]},{"name":"Fondo Sociale Europeo REACT EU\u2014Programma Operativo Nazionale \u201cRicerca e innovazione\u201d 2014\u20132020","award":["433158657"],"award-info":[{"award-number":["433158657"]}]},{"name":"Fondo Sociale Europeo REACT EU\u2014Programma Operativo Nazionale \u201cRicerca e innovazione\u201d 2014\u20132020","award":["Metalli pesanti e degenerazioni retiniche: geni o ambiente?"],"award-info":[{"award-number":["Metalli pesanti e degenerazioni retiniche: geni o ambiente?"]}]},{"name":"Tistou and Charlotte Kerstan Foundation","award":["418081722"],"award-info":[{"award-number":["418081722"]}]},{"name":"Tistou and Charlotte Kerstan Foundation","award":["433158657"],"award-info":[{"award-number":["433158657"]}]},{"name":"Tistou and Charlotte Kerstan Foundation","award":["Metalli pesanti e degenerazioni retiniche: geni o ambiente?"],"award-info":[{"award-number":["Metalli pesanti e degenerazioni retiniche: geni o ambiente?"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Biallelic pathogenic variants in TULP1 are mostly associated with severe rod-driven inherited retinal degeneration. In this study, we analyzed clinical heterogeneity in 17 patients and characterized the underlying biallelic variants in TULP1. All patients underwent thorough ophthalmological examinations. Minigene assays and structural analyses were performed to assess the consequences of splice variants and missense variants. Three patients were diagnosed with Leber congenital amaurosis, nine with early onset retinitis pigmentosa, two with retinitis pigmentosa with an onset in adulthood, one with cone dystrophy, and two with cone-rod dystrophy. Seventeen different alleles were identified, namely eight missense variants, six nonsense variants, one in-frame deletion variant, and two splice site variants. For the latter two, minigene assays revealed aberrant transcripts containing frameshifts and premature termination codons. Structural analysis and molecular modeling suggested different degrees of structural destabilization for the missense variants. In conclusion, we report the largest cohort of patients with TULP1-associated IRD published to date. Most of the patients exhibited rod-driven disease, yet a fraction of the patients exhibited cone-driven disease. Our data support the hypothesis that TULP1 variants do not fold properly and thus trigger unfolded protein response, resulting in photoreceptor death.<\/jats:p>","DOI":"10.3390\/ijms24032709","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T02:52:02Z","timestamp":1675219922000},"page":"2709","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Biallelic Variants in TULP1 Are Associated with Heterogeneous Phenotypes of Retinal Dystrophy"],"prefix":"10.3390","volume":"24","author":[{"given":"Jan-Philipp","family":"Bodenbender","sequence":"first","affiliation":[{"name":"Department for Ophthalmology, University Eye Hospital, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7821-3717","authenticated-orcid":false,"given":"Valerio","family":"Marino","sequence":"additional","affiliation":[{"name":"Section of Biological Chemistry, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37124 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leon","family":"Bethge","sequence":"additional","affiliation":[{"name":"Department for Ophthalmology, University Eye Hospital, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8132-911X","authenticated-orcid":false,"given":"Katarina","family":"Stingl","sequence":"additional","affiliation":[{"name":"Department for Ophthalmology, University Eye Hospital, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6033-4836","authenticated-orcid":false,"given":"Tobias B.","family":"Haack","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Applied Genomics, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Centre for Rare Diseases, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saskia","family":"Biskup","sequence":"additional","affiliation":[{"name":"Praxis f\u00fcr Humangenetik, 72076 T\u00fcbingen, Germany"},{"name":"CeGaT GmbH, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6438-6331","authenticated-orcid":false,"given":"Susanne","family":"Kohl","sequence":"additional","affiliation":[{"name":"Department for Ophthalmology, Institute for Ophthalmic Research, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1906-8681","authenticated-orcid":false,"given":"Laura","family":"K\u00fchlewein","sequence":"additional","affiliation":[{"name":"Department for Ophthalmology, University Eye Hospital, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3724-3044","authenticated-orcid":false,"given":"Daniele","family":"Dell\u2019Orco","sequence":"additional","affiliation":[{"name":"Section of Biological Chemistry, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37124 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1047-6227","authenticated-orcid":false,"given":"Nicole","family":"Weisschuh","sequence":"additional","affiliation":[{"name":"Department for Ophthalmology, Institute for Ophthalmic Research, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,31]]},"reference":[{"key":"ref_1","first-page":"153","article-title":"Epidemiology and prevalence of hereditary retinal dystrophies in the Northern France","volume":"14","author":"Puech","year":"1991","journal-title":"J. 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