{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:31:58Z","timestamp":1790688718786,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,4,27]],"date-time":"2020-04-27T00:00:00Z","timestamp":1587945600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R56AR065483"],"award-info":[{"award-number":["R56AR065483"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pigment Cell Melanoma Res"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Skin pigmentation is a highly heterogeneous trait with diverse consequences worldwide. <jats:italic>SLC24A5<\/jats:italic>, encoding a potent K<jats:sup>+<\/jats:sup>\u2010dependent Na<jats:sup>+<\/jats:sup>\/Ca<jats:sup>2+<\/jats:sup> exchanger, is among the known color\u2010coding genes that participate in melanogenesis by maintaining pH in melanosomes. Deficient SLC24A5 activity results in oculocutaneous albinism (OCA) type 6 in humans. In this study, by utilizing a exome sequencing (ES) approach, we identified two new variants [p. (Gly110Arg) and p. (IIe189Ilefs*1)] of <jats:italic>SLC24A5<\/jats:italic> cosegregating with the OCA phenotype, including nystagmus, strabismus, foveal hypoplasia, albinotic fundus, and vision impairment, in three large consanguineous Pakistani families. Both of these variants failed to rescue the pigmentation in zebrafish s<jats:italic>lc24a5<\/jats:italic> morphants, confirming the pathogenic effects of the variants. We also phenotypically characterized a commercially available zebrafish mutant line (<jats:italic>slc24a5<jats:sup>ko<\/jats:sup><\/jats:italic>) that harbors a nonsense (p.Tyr208*) allele of <jats:italic>slc24a5<\/jats:italic>. Similar to morphants, homozygous <jats:italic>slc24a5<jats:sup>ko<\/jats:sup><\/jats:italic> mutants had significantly reduced melanin content and pigmentation. Next, we used these <jats:italic>slc24a5<jats:sup>ko<\/jats:sup><\/jats:italic> zebrafish mutants to test the efficacy of nitisinone, a compound known to increase ocular and fur pigmentation in OCA1 (<jats:italic>TYR<\/jats:italic>) mutant mice. Treatment of <jats:italic>slc24a5<jats:sup>ko<\/jats:sup><\/jats:italic> mutant zebrafish embryos with varying doses of nitisinone did not improve melanin production and pigmentation, suggesting that treatment with nitisinone is unlikely to be therapeutic in OCA6 patients.<\/jats:p>","DOI":"10.1111\/pcmr.12879","type":"journal-article","created":{"date-parts":[[2020,4,10]],"date-time":"2020-04-10T02:49:27Z","timestamp":1586486967000},"page":"556-565","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Molecular characterization of <i>SLC24A5<\/i> variants and evaluation of Nitisinone treatment efficacy in a zebrafish model of OCA6"],"prefix":"10.1111","volume":"33","author":[{"given":"Sairah","family":"Yousaf","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery School of Medicine University of Maryland Baltimore MD USA"},{"name":"Institute of Molecular Biology &amp; Biotechnology Bahauddin Zakariya University Multan Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saumil","family":"Sethna","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery School of Medicine University of Maryland Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad A.","family":"Chaudhary","sequence":"additional","affiliation":[{"name":"Ophthalmology Department Nishtar Hospital Multan Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rehan S.","family":"Shaikh","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology &amp; Biotechnology Bahauddin Zakariya University Multan Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saima","family":"Riazuddin","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery School of Medicine University of Maryland Baltimore MD USA"},{"name":"Department of Biochemistry and Molecular Biology School of Medicine University of Maryland Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2914-4502","authenticated-orcid":false,"given":"Zubair M.","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery School of Medicine University of Maryland Baltimore MD USA"},{"name":"Department of Biochemistry and Molecular Biology School of Medicine University of Maryland Baltimore MD USA"},{"name":"Department of Ophthalmology and Visual Sciences School of Medicine University of Maryland Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,4,27]]},"reference":[{"key":"e_1_2_9_2_1","article-title":"One\u2010year pilot study on the effects of nitisinone on melanin in patients with OCA\u20101B. JCI","volume":"4","author":"Adams D. R.","year":"2019","journal-title":"Insight"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003912"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12425"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004270000125"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.11.016"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0296-7"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2147\/TACG.S113310"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.01.006"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/ahg.12307"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.728824"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-7-44"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1116238"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12688"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2012.09.012"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2013.360"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI59372"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1086\/522235"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.30036"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2015.11.012"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2013.49"},{"key":"e_1_2_9_22_1","first-page":"212","article-title":"Mutation analysis of two pedigrees with suspected oculocutaneous albinism","volume":"36","author":"Ye H.","year":"2019","journal-title":"Zhonghua Yi Xue Yi Chuan Xue Za Zhi"}],"container-title":["Pigment Cell &amp; Melanoma Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fpcmr.12879","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pcmr.12879","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/pcmr.12879","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pcmr.12879","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T05:37:43Z","timestamp":1693978663000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/pcmr.12879"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,27]]},"references-count":21,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,7]]}},"alternative-id":["10.1111\/pcmr.12879"],"URL":"https:\/\/doi.org\/10.1111\/pcmr.12879","archive":["Portico"],"relation":{},"ISSN":["1755-1471","1755-148X"],"issn-type":[{"value":"1755-1471","type":"print"},{"value":"1755-148X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,27]]},"assertion":[{"value":"2020-01-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}