{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T04:30:04Z","timestamp":1772166604341,"version":"3.50.1"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T00:00:00Z","timestamp":1736812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T00:00:00Z","timestamp":1736812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100010457","name":"Centre Hospitalier Universitaire de Bordeaux","doi-asserted-by":"publisher","award":["no number"],"award-info":[{"award-number":["no number"]}],"id":[{"id":"10.13039\/501100010457","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Hum Genet"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Pigmentation is orchestrated by hundreds of genes involved in cellular functions going from early developmental fate of pigment cells to melanin synthesis. The Two Pore Channel 2 (TPC2) a Ca2+ and Na+ channel acidifies melanosomal pH and thus inhibits pigmentation. A young patient was recently reported with generalized hypopigmentation but uneventful ocular examination, caused by the de novo heterozygous <jats:italic>TPCN2<\/jats:italic> variant c.628C&gt;T;p.Arg210Cys that constitutively activates TPC2. Here we report a young patient with the same de novo variant presenting with generalized hypopigmentation, and ophthalmologic features including low grade retinal hypopigmentation and foveal hypoplasia, photophobia, mild hypermetropia, and astigmatism, which are features of albinism. Skin fragility and episodes of fever with diarrhea and fatigue were also observed. This extends the phenotype of patients with <jats:italic>TPCN2<\/jats:italic> variants, warranting further investigations in patients with alterations of this gene, and raises the question whether <jats:italic>TPCN2<\/jats:italic> might be considered as an albinism gene.<\/jats:p>","DOI":"10.1038\/s41431-024-01779-5","type":"journal-article","created":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T13:27:14Z","timestamp":1736861234000},"page":"383-386","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A patient with TPCN2-related hypopigmentation and ocular phenotype"],"prefix":"10.1038","volume":"33","author":[{"given":"C\u00e9cile","family":"Courdier","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5788-392X","authenticated-orcid":false,"given":"Vincent","family":"Michaud","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Modibo","family":"Diallo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1293-6717","authenticated-orcid":false,"given":"Claudio","family":"Plaisant","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eulalie","family":"Lasseaux","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Helot","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elodie","family":"Philippe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Els","family":"Vrielynck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2959-0935","authenticated-orcid":false,"given":"Marjolaine","family":"Willems","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2987-2932","authenticated-orcid":false,"given":"Benoit","family":"Arveiler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,1,14]]},"reference":[{"key":"1779_CR1","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1111\/pcmr.12743","volume":"32","author":"LL Baxter","year":"2019","unstructured":"Baxter LL, Watkins\u2010Chow DE, Pavan WJ, Loftus SK. A curated gene list for expanding the horizons of pigmentation biology. Pigment Cell Melanoma Res. 2019;32:348\u201358.","journal-title":"Pigment Cell Melanoma Res"},{"key":"1779_CR2","doi-asserted-by":"publisher","first-page":"1517","DOI":"10.1093\/icb\/icab078","volume":"61","author":"L Le","year":"2021","unstructured":"Le L, Sir\u00e9s-Campos J, Raposo G, Delevoye C, Marks MS. Melanosome Biogenesis in the Pigmentation of Mammalian Skin. Integr Comp Biol. 2021;61:1517\u201345. https:\/\/doi.org\/10.1093\/icb\/icab078","journal-title":"Integr Comp Biol"},{"key":"1779_CR3","doi-asserted-by":"crossref","unstructured":"Lasseaux E, Neveu MM, Fiore M, Morice-Picard F, Arveiler B. Albinism. In Clinical Ophthalmic Genetics and Genomics. 2022. https:\/\/www.elsevier.com\/books-and-journals.","DOI":"10.1016\/B978-0-12-813944-8.00018-4"},{"key":"1779_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2022.101091","volume":"91","author":"R Bakker","year":"2022","unstructured":"Bakker R, Wagstaff EL, Kruijt CC, Emri E, van Karnebeek CDM, Hoffmann MB, et al. The retinal pigmentation pathway in human albinism: Not so black and white. Prog Retin Eye Res. 2022;91:101091.","journal-title":"Prog Retin Eye Res"},{"key":"1779_CR5","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1016\/j.ajhg.2019.04.008","volume":"104","author":"E-R Nicoli","year":"2019","unstructured":"Nicoli E-R, Weston MR, Hackbarth M, Becerril A, Larson A, Zein WM, et al. Lysosomal Storage and Albinism Due to Effects of a De Novo CLCN7 Variant on Lysosomal Acidification. 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Two newly identified genetic determinants of pigmentation in Europeans. Nat Genet 2008;40:835\u20137.","journal-title":"Nat Genet"},{"key":"1779_CR9","doi-asserted-by":"publisher","first-page":"E8595","DOI":"10.1073\/pnas.1705739114","volume":"114","author":"YK Chao","year":"2017","unstructured":"Chao YK, Schludi V, Chen CC, Butz E, Nguyen ONP, M\u00fcller M, et al. TPC2 polymorphisms associated with a hair pigmentation phenotype in humans result in gain of channel function by independent mechanisms. Proc Nat Acad Sci USA. 2017;114:E8595.","journal-title":"Proc Nat Acad Sci USA"},{"key":"1779_CR10","doi-asserted-by":"publisher","first-page":"e1009236","DOI":"10.1371\/journal.pgen.1009236","volume":"17","author":"J B\u00f6ck","year":"2021","unstructured":"B\u00f6ck J, Krogsaeter E, Passon M, Chao YK, Sharma S, Grallert H, et al. Human genome diversity data reveal that L564P is the predominant TPC2 variant and a prerequisite for the blond hair associated M484L gain-of-function effect. 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This study was approved by the Comit\u00e9 de Protection des Personnes Sud Ouest et Outre Mer III and performed according to the Declaration of Helsinki. Consent to publish photographs of the patient and his parents was obtained.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}