{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T22:52:18Z","timestamp":1781823138679,"version":"3.54.5"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006005","name":"Agence de la Biom\u00e9decine","doi-asserted-by":"publisher","award":["21AMP011"],"award-info":[{"award-number":["21AMP011"]}],"id":[{"id":"10.13039\/501100006005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["OCAGEN: ANR-21-CE17-0041-01"],"award-info":[{"award-number":["OCAGEN: ANR-21-CE17-0041-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>\n                    The molecular diagnosis of albinism is hampered by a significant number of genetic variants of unknown significance (VUS) including a majority of missense and in-frame insertion deletion variants. This contributes to the high rate of unresolved genetic diagnosis for this disease. We designed a straightforward test of missense VUS in albinism genes based on functional rescue. As a proof of concept, the assay was set up for testing variants in the\n                    <jats:italic>TYR<\/jats:italic>\n                    gene associated with oculocutaneous albinism type 1. The\n                    <jats:italic>TYR<\/jats:italic>\n                    gene was knocked-out in the human melanogenic MNT1 cell line and the resulting unpigmented clones used as host cells for rescue experiments. Selected VUS and control sequences were run through the assay. Expression of tyrosinase was quantified by Western blot, melanin synthesis was evaluated by direct observation as well as absorbance monitoring. One VUS, p.Ser270Phe (S270F) can be classified as likely pathogenic as it fails to restore pigmentation, whereas rescue was achieved with D305E and A391T. The two most frequent missense VUS of\n                    <jats:italic>TYR<\/jats:italic>\n                    , S192Y and R402Q, were also tested independently or in combination confirming the pathogenic effect of their association in\n                    <jats:italic>cis<\/jats:italic>\n                    . All in all, this new assay is a proof of concept and can be considered for testing variants in other albinism genes such as\n                    <jats:italic>TYRP1<\/jats:italic>\n                    and\n                    <jats:italic>SLC45A2<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.3389\/fgene.2026.1821461","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T22:10:25Z","timestamp":1781820625000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A rescue assay for genetic diagnosis of oculocutaneous albinism using melanocytic MNT1 knock-out cells"],"prefix":"10.3389","volume":"17","author":[{"given":"Elina","family":"Mercier","sequence":"first","affiliation":[{"name":"Rare Diseases Genetics and Metabolism, INSERM U1211, University of Bordeaux","place":["Bordeaux, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Michaud","sequence":"additional","affiliation":[{"name":"Rare Diseases Genetics and Metabolism, INSERM U1211, University of Bordeaux","place":["Bordeaux, France"]},{"name":"Molecular Genetics Laboratory, Bordeaux University Hospital","place":["Bordeaux, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ang\u00e8le","family":"Sequeira","sequence":"additional","affiliation":[{"name":"Rare Diseases Genetics and Metabolism, INSERM U1211, University of Bordeaux","place":["Bordeaux, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Arveiler","sequence":"additional","affiliation":[{"name":"Rare Diseases Genetics and Metabolism, INSERM U1211, University of Bordeaux","place":["Bordeaux, France"]},{"name":"Molecular Genetics Laboratory, Bordeaux University Hospital","place":["Bordeaux, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Javerzat","sequence":"additional","affiliation":[{"name":"Rare Diseases Genetics and Metabolism, INSERM U1211, University of Bordeaux","place":["Bordeaux, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"101091","DOI":"10.1016\/j.preteyeres.2022.101091","article-title":"The retinal pigmentation pathway in human albinism: not so black and white","volume":"91","author":"Bakker","year":"2022","journal-title":"Prog. 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