{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T13:39:31Z","timestamp":1776433171923,"version":"3.51.2"},"reference-count":13,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T00:00:00Z","timestamp":1719360000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T00:00:00Z","timestamp":1719360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Shaanxi Natural Science Basic research Program","award":["S2020-JC-YB-0446"],"award-info":[{"award-number":["S2020-JC-YB-0446"]}]},{"name":"Shaanxi Natural Science Basic research Program","award":["S2020-JC-YB-0446"],"award-info":[{"award-number":["S2020-JC-YB-0446"]}]},{"DOI":"10.13039\/501100018611","name":"International Science and Technology Cooperation Program of Shanxi Province","doi-asserted-by":"publisher","award":["2022KG-22"],"award-info":[{"award-number":["2022KG-22"]}],"id":[{"id":"10.13039\/501100018611","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To analyse the genetic aetiology of a child with oculocutaneous albinism and to explore the effects of two mutation sites on the function of the OCA2 protein at the mRNA and protein levels via the use of recombinant carriers in vitro. Whole-exome sequencing (WES) and Sanger sequencing were used to analyse the pathogenic genes of the child and validate the mutations in the parents. pEGFP and phage vectors carrying wild-type and mutant <jats:italic>OCA2<\/jats:italic> were constructed using the coding DNA sequence (CDS) of the whole gene-synthesized <jats:italic>OCA2<\/jats:italic> as a template and transfected into HEK293T cells, after which expression analysis was performed. The child in this study was born with white skin, hair, eyelashes, and eyebrows and exhibited nystagmus. Genetic analysis indicated that the child carried two heterozygous mutations: c.1079C\u2009&gt;\u2009T (p.Ser360Phe) of maternal origin and c.1095_1103delAGCACTGGC (p.Ala366_Ala368del) of paternal origin, conforming to an autosomal recessive inheritance pattern. In vitro analysis showed that the expression of the c.1079C\u2009&gt;\u2009T (p.Ser360Phe) mutant did not significantly change at the mRNA level but did increase at the protein level, suggesting that the mutation may lead to enhanced protein stability, and the c.1095_1103delAGCACTGGC (p.Ala366_Ala368del) mutation resulted in the loss of three amino acids in exon 10, producing a truncated protein. In vitro expression analysis also revealed that the expression of the mutant gene was significantly downregulated at both the mRNA and protein levels, suggesting that the mutation can simultaneously produce truncated proteins and lead to protein degradation. This case study enriches the phenotypic spectrum of <jats:italic>OCA2<\/jats:italic> gene disease. In vitro expression analysis confirmed that both mutations affect protein expression, providing a theoretical basis for analysing the pathogenicity of these two mutations.<\/jats:p>","DOI":"10.1038\/s41598-024-64782-2","type":"journal-article","created":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T18:08:08Z","timestamp":1719425288000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Functional analysis of two mutation sites in the OCA2 gene"],"prefix":"10.1038","volume":"14","author":[{"given":"XiaoHua","family":"Yuan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qun","family":"Dang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue Lan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,6,26]]},"reference":[{"key":"64782_CR1","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1111\/pcmr.12790","volume":"32","author":"Z Zhong","year":"2019","unstructured":"Zhong, Z. et al. Comprehensive analysis of spectral distribution of a large cohort of Chinese patients with non-syndromic oculocutaneous albinism facilitates genetic diagnosis. Pigment Cell Melanoma Res. 32, 672\u2013686. https:\/\/doi.org\/10.1111\/pcmr.12790 (2019).","journal-title":"Pigment Cell Melanoma Res."},{"key":"64782_CR2","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1111\/cge.12019","volume":"84","author":"T Kausar","year":"2013","unstructured":"Kausar, T. et al. OCA5, a novel locus for non-syndromic oculocutaneous albinism, maps to chromosome 4q24. Clin. Genet. 84, 91\u201393. https:\/\/doi.org\/10.1111\/cge.12019 (2013).","journal-title":"Clin. Genet."},{"key":"64782_CR3","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards, S. et al. Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet. Med. 17, 405\u2013424. https:\/\/doi.org\/10.1038\/gim.2015.30 (2015).","journal-title":"Genet. Med."},{"key":"64782_CR4","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.687","volume":"7","author":"Y Lin","year":"2019","unstructured":"Lin, Y. et al. Mutational analysis of TYR, OCA2, and SLC45A2 genes in Chinese families with oculocutaneous albinism. Mol. Genet. Genomic Med. 7, e00687. https:\/\/doi.org\/10.1002\/mgg3.687 (2019).","journal-title":"Mol. Genet. Genomic Med."},{"key":"64782_CR5","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1111\/pcmr.12688","volume":"31","author":"E Lasseaux","year":"2018","unstructured":"Lasseaux, E. et al. Molecular characterization of a series of 990 index patients with albinism. Pigment Cell Melanoma Res. 31, 466\u2013474. https:\/\/doi.org\/10.1111\/pcmr.12688 (2018).","journal-title":"Pigment Cell Melanoma Res."},{"key":"64782_CR6","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/905472","volume":"2014","author":"B Kamaraj","year":"2014","unstructured":"Kamaraj, B. & Purohit, R. Mutational analysis of oculocutaneous albinism: A compact review. Biomed. Res. Int. 2014, 905472. https:\/\/doi.org\/10.1155\/2014\/905472 (2014).","journal-title":"Biomed. Res. Int."},{"key":"64782_CR7","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1002\/(sici)1098-1004(200002)15:2<166::Aid-humu5>3.0.Co;2-z","volume":"15","author":"R Kerr","year":"2000","unstructured":"Kerr, R. et al. Identification of P gene mutations in individuals with oculocutaneous albinism in sub-Saharan Africa. Hum. Mutat. 15, 166\u2013172. https:\/\/doi.org\/10.1002\/(sici)1098-1004(200002)15:2%3c166::Aid-humu5%3e3.0.Co;2-z (2000).","journal-title":"Hum. Mutat."},{"key":"64782_CR8","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1007\/s11010-015-2337-y","volume":"403","author":"S Park","year":"2015","unstructured":"Park, S. et al. Unrevealing the role of P-protein on melanosome biology and structure, using siRNA-mediated down regulation of OCA2. Mol. Cell Biochem. 403, 61\u201371. https:\/\/doi.org\/10.1007\/s11010-015-2337-y (2015).","journal-title":"Mol. Cell Biochem."},{"key":"64782_CR9","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.04543","volume":"3","author":"NW Bellono","year":"2014","unstructured":"Bellono, N. W. et al. An intracellular anion channel critical for pigmentation. Elife 3, e04543. https:\/\/doi.org\/10.7554\/eLife.04543 (2014).","journal-title":"Elife"},{"key":"64782_CR10","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1034\/j.1600-0749.2001.140203.x","volume":"14","author":"MH Brilliant","year":"2001","unstructured":"Brilliant, M. H. The mouse p (pink-eyed dilution) and human P genes, oculocutaneous albinism type 2 (OCA2), and melanosomal pH. Pigment Cell Res. 14, 86\u201393. https:\/\/doi.org\/10.1034\/j.1600-0749.2001.140203.x (2001).","journal-title":"Pigment Cell Res."},{"key":"64782_CR11","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/j.tig.2004.06.010","volume":"20","author":"RA Sturm","year":"2004","unstructured":"Sturm, R. A. & Frudakis, T. N. Eye colour: Portals into pigmentation genes and ancestry. Trends Genet. 20, 327\u2013332. https:\/\/doi.org\/10.1016\/j.tig.2004.06.010 (2004).","journal-title":"Trends Genet."},{"key":"64782_CR12","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1101\/gr.128652.111","volume":"22","author":"M Visser","year":"2012","unstructured":"Visser, M., Kayser, M. & Palstra, R. J. HERC2 rs12913832 modulates human pigmentation by attenuating chromatin-loop formation between a long-range enhancer and the OCA2 promoter. 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