{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:13:28Z","timestamp":1792512808482,"version":"4.5.0"},"reference-count":62,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T00:00:00Z","timestamp":1649808000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013875","name":"Retina France","doi-asserted-by":"publisher","award":["2019"],"award-info":[{"award-number":["2019"]}],"id":[{"id":"10.13039\/501100013875","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Biallelic gene defects in MFSD8 are not only a cause of the late-infantile form of neuronal ceroid lipofuscinosis, but also of rare isolated retinal degeneration. We report clinical and genetic data of seven patients compound heterozygous or homozygous for variants in MFSD8, issued from a French cohort with inherited retinal degeneration, and two additional patients retrieved from a Swiss cohort. Next-generation sequencing of large panels combined with whole-genome sequencing allowed for the identification of twelve variants from which seven were novel. Among them were one deep intronic variant c.998+1669A&gt;G, one large deletion encompassing exon 9 and 10, and a silent change c.750A&gt;G. Transcript analysis performed on patients\u2019 lymphoblastoid cell lines revealed the creation of a donor splice site by c.998+1669A&gt;G, resulting in a 140 bp pseudoexon insertion in intron 10. Variant c.750A&gt;G produced exon 8 skipping. In silico and in cellulo studies of these variants allowed us to assign the pathogenic effect, and showed that the combination of at least one severe variant with a moderate one leads to isolated retinal dystrophy, whereas the combination in trans of two severe variants is responsible for early onset severe retinal dystrophy in the context of late-infantile neuronal ceroid lipofuscinosis.<\/jats:p>","DOI":"10.3390\/ijms23084294","type":"journal-article","created":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T21:33:42Z","timestamp":1649885622000},"page":"4294","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Contribution of Whole-Genome Sequencing and Transcript Analysis to Decipher Retinal Diseases Associated with MFSD8 Variants"],"prefix":"10.3390","volume":"23","author":[{"given":"Ana\u00efs F.","family":"Poncet","sequence":"first","affiliation":[{"name":"Univ. Lille, Inserm, CHU Lille, U1172-LilNCog-Lille Neuroscience & Cognition, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9845-948X","authenticated-orcid":false,"given":"Olivier","family":"Grunewald","sequence":"additional","affiliation":[{"name":"Univ. Lille, Inserm, CHU Lille, U1172-LilNCog-Lille Neuroscience & Cognition, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Vaclavik","sequence":"additional","affiliation":[{"name":"University of Lausanne, Jules-Gonin Eye Hospital, 1004 Lausanne, Switzerland"},{"name":"Cantonal Hospital, Department of Ophthalmology, 1700 Fribourg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Meunier","sequence":"additional","affiliation":[{"name":"National Reference Centre for Inherited Sensory Diseases, University of Montpellier, Montpellier University Hospital, Sensgene Care Network, ERN-EYE Network, F-34000 Montpellier, France"},{"name":"Institute for Neurosciences of Montpellier (INM), University of Montpellier, INSERM, F-34000 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Drumare","sequence":"additional","affiliation":[{"name":"Exploration de la Vision et Neuro-Ophtalmology, CHU de Lille, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Pelletier","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence pour les Affections Rares en G\u00e9n\u00e9tique Ophtalmologiques, Hopitaux Universitaires de Strasbourg, F-67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6369-4818","authenticated-orcid":false,"given":"B\u00e9atrice","family":"Bocquet","sequence":"additional","affiliation":[{"name":"National Reference Centre for Inherited Sensory Diseases, University of Montpellier, Montpellier University Hospital, Sensgene Care Network, ERN-EYE Network, F-34000 Montpellier, France"},{"name":"Institute for Neurosciences of Montpellier (INM), University of Montpellier, INSERM, F-34000 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita G.","family":"Todorova","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Cantonal Hospital, 9007 St. Gallen, Switzerland"},{"name":"Department of Ophthalmology, University of Z\u00fcrich, 8091 Z\u00fcrich, Switzerland"},{"name":"Department of Ophthalmology, University of Basel, 4056 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Ga\u00eblle","family":"Le Moing","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, Amiens-Picardy University Hospital, F-80000 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurore","family":"Devos","sequence":"additional","affiliation":[{"name":"Univ. Lille, Inserm, CHU Lille, U1172-LilNCog-Lille Neuroscience & Cognition, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1331-504X","authenticated-orcid":false,"given":"Daniel F.","family":"Schorderet","sequence":"additional","affiliation":[{"name":"Faculty of Biology and Medicine, University of Lausanne and Faculty of Life Sciences, Ecole Polytechnique F\u00e9d\u00e9rale of Lausanne, 1004 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4490-8224","authenticated-orcid":false,"given":"Florence","family":"Jobic","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de G\u00e9n\u00e9tique M\u00e9dicale et Oncog\u00e9n\u00e9tique, Centre Hospitalier Universitaire Amiens Picardie, F-80000 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Defoort-Dhellemmes","sequence":"additional","affiliation":[{"name":"Exploration de la Vision et Neuro-Ophtalmology, CHU de Lille, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne","family":"Dollfus","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence pour les Affections Rares en G\u00e9n\u00e9tique Ophtalmologiques, Hopitaux Universitaires de Strasbourg, F-67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasily M.","family":"Smirnov","sequence":"additional","affiliation":[{"name":"Exploration de la Vision et Neuro-Ophtalmology, CHU de Lille, F-59000 Lille, France"},{"name":"Universit\u00e9 de Lille, Facult\u00e9 de M\u00e9decine, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4719-4124","authenticated-orcid":false,"given":"Claire-Marie","family":"Dhaenens","sequence":"additional","affiliation":[{"name":"Univ. 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