{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T02:30:07Z","timestamp":1775269807957,"version":"3.50.1"},"reference-count":33,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2019,10,19]],"date-time":"2019-10-19T00:00:00Z","timestamp":1571443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["TBI-V-1-083-VBW-028"],"award-info":[{"award-number":["TBI-V-1-083-VBW-028"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["TBI-V-1-082-VBW-028"],"award-info":[{"award-number":["TBI-V-1-082-VBW-028"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union Social Fund","award":["ESF\/14-BM-A55-0046\/16"],"award-info":[{"award-number":["ESF\/14-BM-A55-0046\/16"]}]},{"name":"European Union Social Fund","award":["ESF\/14-BM-A55-0045\/16"],"award-info":[{"award-number":["ESF\/14-BM-A55-0045\/16"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Niemann-Pick Type C (NP-C) is a rare disorder of lipid metabolism caused by mutations within the NPC1 and NPC2 genes. NP-C is a neurovisceral disease leading to a heterogeneous, multisystemic spectrum of symptoms in those affected. Until now, there is no investigative tool to demonstrate the significance of single variants within the NPC genes. Hence, the aim of the study was to establish a test that allows for an objective assessment of the pathological potential of NPC1 gene variants. Chinese hamster ovary cells defective in the NPC1 gene accumulate cholesterol in lysosomal storage organelles. The cells were transfected with NPC1-GFP plasmid vectors carrying distinct sequence variants. Filipin staining was used to test for complementation of the phenotype. The known variant p.Ile1061Thr showed a significantly impaired cholesterol clearance after 12 and 24 h compared to the wild type. Among the investigated variants, p.Ser954Leu and p.Glu1273Lys showed decelerated cholesterol clearance as well. The remaining variants p.Gln60His, p.Val494Met, and p.Ile787Val showed a cholesterol clearance indistinguishable from wild type. Further, p.Ile1061Thr acquired an enhanced clearance ability upon 25-hydroxycholesterol treatment. We conclude that the variants that caused an abnormal clearance phenotype are highly likely to be of clinical relevance. Moreover, we present a system that can be utilized to screen for new drugs.<\/jats:p>","DOI":"10.3390\/ijms20205185","type":"journal-article","created":{"date-parts":[[2019,10,21]],"date-time":"2019-10-21T03:40:29Z","timestamp":1571629229000},"page":"5185","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Determination of the Pathological Features of NPC1 Variants in a Cellular Complementation Test"],"prefix":"10.3390","volume":"20","author":[{"given":"Xiao","family":"Feng","sequence":"first","affiliation":[{"name":"Translational Neurodegeneration Section \u201eAlbrecht-Kossel\u201c, Department of Neurology, University Medical Center Rostock, University of Rostock, 18147 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Cozma","sequence":"additional","affiliation":[{"name":"Centogene AG, 18055 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9630-1999","authenticated-orcid":false,"given":"Supansa","family":"Pantoom","sequence":"additional","affiliation":[{"name":"Translational Neurodegeneration Section \u201eAlbrecht-Kossel\u201c, Department of Neurology, University Medical Center Rostock, University of Rostock, 18147 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Hund","sequence":"additional","affiliation":[{"name":"Translational Neurodegeneration Section \u201eAlbrecht-Kossel\u201c, Department of Neurology, University Medical Center Rostock, University of Rostock, 18147 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Iwanov","sequence":"additional","affiliation":[{"name":"Translational Neurodegeneration Section \u201eAlbrecht-Kossel\u201c, Department of Neurology, University Medical Center Rostock, University of Rostock, 18147 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janine","family":"Petters","sequence":"additional","affiliation":[{"name":"Translational Neurodegeneration Section \u201eAlbrecht-Kossel\u201c, Department of Neurology, University Medical Center Rostock, University of Rostock, 18147 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christin","family":"V\u00f6lkner","sequence":"additional","affiliation":[{"name":"Translational Neurodegeneration Section \u201eAlbrecht-Kossel\u201c, Department of Neurology, University Medical Center Rostock, University of Rostock, 18147 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Bauer","sequence":"additional","affiliation":[{"name":"Centogene AG, 18055 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian","family":"Vogel","sequence":"additional","affiliation":[{"name":"Centogene AG, 18055 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Bauer","sequence":"additional","affiliation":[{"name":"Centogene AG, 18055 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank U.","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Medicine A, University Medicine Greifswald, 17489 Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus M.","family":"Lerch","sequence":"additional","affiliation":[{"name":"Department of Medicine A, University Medicine Greifswald, 17489 Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne-Marie","family":"Knospe","sequence":"additional","affiliation":[{"name":"Translational Neurodegeneration Section \u201eAlbrecht-Kossel\u201c, Department of Neurology, University Medical Center Rostock, University of Rostock, 18147 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7364-7791","authenticated-orcid":false,"given":"Andreas","family":"Hermann","sequence":"additional","affiliation":[{"name":"Translational Neurodegeneration Section \u201eAlbrecht-Kossel\u201c, Department of Neurology, University Medical Center Rostock, University of Rostock, 18147 Rostock, Germany"},{"name":"Center for Transdisciplinary Neurosciences Rostock (CTNR), Rostock University Medical Center, University of Rostock, 18147 Rostock, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE), Research side Rostock, 18147 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2421-8779","authenticated-orcid":false,"given":"Moritz J.","family":"Frech","sequence":"additional","affiliation":[{"name":"Translational Neurodegeneration Section \u201eAlbrecht-Kossel\u201c, Department of Neurology, University Medical Center Rostock, University of Rostock, 18147 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiankai","family":"Luo","sequence":"additional","affiliation":[{"name":"Translational Neurodegeneration Section \u201eAlbrecht-Kossel\u201c, Department of Neurology, University Medical Center Rostock, University of Rostock, 18147 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arndt","family":"Rolfs","sequence":"additional","affiliation":[{"name":"Centogene AG, 18055 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Lukas","sequence":"additional","affiliation":[{"name":"Translational Neurodegeneration Section \u201eAlbrecht-Kossel\u201c, Department of Neurology, University Medical Center Rostock, University of Rostock, 18147 Rostock, Germany"},{"name":"Center for Transdisciplinary Neurosciences Rostock (CTNR), Rostock University Medical Center, University of Rostock, 18147 Rostock, 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