{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T23:55:35Z","timestamp":1793663735802,"version":"4.5.1"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,6,30]],"date-time":"2017-06-30T00:00:00Z","timestamp":1498780800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,6,30]],"date-time":"2017-06-30T00:00:00Z","timestamp":1498780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Oculocutaneous albinism (OCA) and ocular albinism (OA) are inherited disorders of melanin biosynthesis, resulting in loss of pigment and severe visual deficits. OCA encompasses a range of subtypes with overlapping, often hypomorphic phenotypes. OCA1 is the most common cause of albinism in European populations and is inherited through autosomal recessive mutations in the Tyrosinase (<jats:italic>TYR)<\/jats:italic> gene. However, there is a high level of reported missing heritability, where only a single heterozygous mutation is found in <jats:italic>TYR<\/jats:italic>. This is also the case for other OCA subtypes including OCA2 caused by mutations in the <jats:italic>OCA2<\/jats:italic> gene. Here we have interrogated the genetic cause of albinism in a well phenotyped, hypomorphic albinism population by sequencing a broad gene panel and performing segregation studies on phenotyped family members. Of eighteen probands we can confidently diagnose three with OA and OCA2, and one with a <jats:italic>PAX6<\/jats:italic> mutation. Of six probands with only a single heterozygous mutation in <jats:italic>TYR<\/jats:italic>, all were found to have the two common variants S192Y and R402Q. Our results suggest that a combination of R402Q and S192Y with a deleterious mutation in a \u2018tri-allelic genotype\u2019 can account for missing heritability in some hypomorphic OCA1 albinism phenotypes.<\/jats:p>","DOI":"10.1038\/s41598-017-04401-5","type":"journal-article","created":{"date-parts":[[2017,6,26]],"date-time":"2017-06-26T09:34:52Z","timestamp":1498469692000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Identification of a functionally significant tri-allelic genotype in the Tyrosinase gene (TYR) causing hypomorphic oculocutaneous albinism (OCA1B)"],"prefix":"10.1038","volume":"7","author":[{"given":"Chelsea S.","family":"Norman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke","family":"O\u2019Gorman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0973-8285","authenticated-orcid":false,"given":"Jane","family":"Gibson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reuben J.","family":"Pengelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3217-4833","authenticated-orcid":false,"given":"Diana","family":"Baralle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Arjuna","family":"Ratnayaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Griffiths","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Rose-Zerilli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Ranger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Bunyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhiannon","family":"Page","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tutte","family":"Newall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima","family":"Shawkat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Mattocks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Ward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Ennis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1030-9963","authenticated-orcid":false,"given":"Jay E.","family":"Self","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,6,30]]},"reference":[{"key":"4401_CR1","doi-asserted-by":"publisher","first-page":"b25","DOI":"10.1186\/1750-1172-2-43","volume":"2","author":"K Gr\u00f8nskov","year":"2007","unstructured":"Gr\u00f8nskov, K., Ek, J. & Brondum-Nielsen, K. Oculocutaneous albinism. Orphanet J. Rare Dis. \n                           2, b25 (2007).","journal-title":"Orphanet J. Rare Dis."},{"key":"4401_CR2","doi-asserted-by":"publisher","first-page":"1653","DOI":"10.1016\/j.ophtha.2011.01.028","volume":"118","author":"MG Thomas","year":"2011","unstructured":"Thomas, M. G. et al. Structural grading of foveal hypoplasia using spectral-domain optical coherence tomography: a predictor of visual acuity? Ophthalmology \n                           118, 1653\u20131660 (2011).","journal-title":"Ophthalmology"},{"key":"4401_CR3","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1136\/bjo.87.6.767","volume":"87","author":"S Dorey","year":"2003","unstructured":"Dorey, S., Neveu, M., Burton, L., Sloper, J. & Holder, G. The clinical features of albinism and their correlation with visual evoked potentials. Br. J. Ophthalmol \n                           87, 767\u2013772 (2003).","journal-title":"Br. J. Ophthalmol"},{"key":"4401_CR4","doi-asserted-by":"publisher","first-page":"167","DOI":"10.3928\/01913913-20150427-06","volume":"52","author":"BK McCafferty","year":"2015","unstructured":"McCafferty, B. K. et al. Clinical Insights Into Foveal Morphology in Albinism. J. Pediatr. Ophthalmol. Strabismus \n                           52, 167\u2013172, doi:10.3928\/01913913-20150427-06 (2015).","journal-title":"J. Pediatr. Ophthalmol. Strabismus"},{"key":"4401_CR5","doi-asserted-by":"crossref","unstructured":"Wolf, A. B., Rubin, S. E. & Kodsi, S. R. Comparison of Clinical Findings in Pediatric Patients With Albinism and Different Amplitudes of Nystagmus. Journal of American Association for Pediatric Ophthalmology and Strabismus \n                           9, 363\u2013368, doi:http:\/\/dx.doi.org\/10.1016\/j.jaapos.2005.03.003 (2005).","DOI":"10.1016\/j.jaapos.2005.03.003"},{"key":"4401_CR6","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1111\/pcmr.12167","volume":"27","author":"L Montoliu","year":"2014","unstructured":"Montoliu, L. et al. Increasing the complexity: new genes and new types of albinism. Pigment Cell & Melanoma Research \n                           27, 11\u201318, doi:10.1111\/pcmr.12167 (2014).","journal-title":"Pigment Cell & Melanoma Research"},{"key":"4401_CR7","doi-asserted-by":"crossref","unstructured":"Oetting, W. S. & King, R. A. Molecular basis of albinism: mutations and polymorphisms of pigmentation genes associated with albinism. Hum. Mutat. 13, 99\u2013115, doi:10.1002\/(sici)1098-1004(1999)13:2<99::aid-humu2>3.0.co;2-c (1999).","DOI":"10.1002\/(SICI)1098-1004(1999)13:2<99::AID-HUMU2>3.0.CO;2-C"},{"key":"4401_CR8","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1007\/s00439-003-0998-1","volume":"113","author":"R King","year":"2003","unstructured":"King, R. et al. Tyrosinase gene mutations in oculocutaneous albinism 1 (OCA1): definition of the phenotype. Hum. Genet. \n                           113, 502\u2013513, doi:10.1007\/s00439-003-0998-1 (2003).","journal-title":"Hum. Genet."},{"key":"4401_CR9","doi-asserted-by":"publisher","first-page":"2581","DOI":"10.1167\/iovs.08-2827","volume":"50","author":"M Hingorani","year":"2009","unstructured":"Hingorani, M., Williamson, K. A., Moore, A. T. & van Heyningen, V. Detailed ophthalmologic evaluation of 43 individuals with PAX6 mutations. Invest. Ophthalmol. Vis. Sci. \n                           50, 2581\u20132590, doi:10.1167\/iovs.08-2827 (2009).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"4401_CR10","doi-asserted-by":"publisher","first-page":"2442","DOI":"10.1038\/jid.2008.109","volume":"128","author":"SM Hutton","year":"2008","unstructured":"Hutton, S. M. & Spritz, R. A. Comprehensive analysis of oculocutaneous albinism among non-Hispanic caucasians shows that OCA1 is the most prevalent OCA type. J. Invest. Dermatol. \n                           128, 2442\u20132450 (2008a).","journal-title":"J. Invest. Dermatol."},{"key":"4401_CR11","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.1167\/iovs.10-6091","volume":"52","author":"A Gargiulo","year":"2011","unstructured":"Gargiulo, A. et al. Molecular and clinical characterization of albinism in a large cohort of Italian patients. Invest. Ophthalmol. Vis. Sci. \n                           52, 1281\u20131289, doi:10.1167\/iovs.10-6091 (2011).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"4401_CR12","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1002\/humu.22315","volume":"34","author":"DR Simeonov","year":"2013","unstructured":"Simeonov, D. R. et al. DNA Variations in Oculocutaneous Albinism: An Updated Mutation List and Current Outstanding Issues in Molecular Diagnostics. Hum. Mutat. \n                           34, 827\u2013835, doi:10.1002\/humu.22315 (2013).","journal-title":"Hum. Mutat."},{"key":"4401_CR13","doi-asserted-by":"publisher","first-page":"1493","DOI":"10.1002\/ajmg.a.32321","volume":"146A","author":"P-W Chiang","year":"2008","unstructured":"Chiang, P.-W., Spector, E. & Tsai, A. C.-H. Evidence suggesting the inheritance mode of the human P gene in skin complexion is not strictly recessive. American Journal of Medical Genetics Part A \n                           146A, 1493\u20131496, doi:10.1002\/ajmg.a.32321 (2008a).","journal-title":"American Journal of Medical Genetics Part A"},{"key":"4401_CR14","doi-asserted-by":"publisher","first-page":"2427","DOI":"10.1002\/ajmg.a.32453","volume":"146A","author":"P-W Chiang","year":"2008","unstructured":"Chiang, P.-W., Fulton, A. B., Spector, E. & Hisama, F. M. Synergistic interaction of the OCA2 and OCA3 genes in a family. American Journal of Medical Genetics Part A \n                           146A, 2427\u20132430, doi:10.1002\/ajmg.a.32453 (2008b).","journal-title":"American Journal of Medical Genetics Part A"},{"key":"4401_CR15","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1111\/pcmr.12253","volume":"27","author":"K Jagirdar","year":"2014","unstructured":"Jagirdar, K. et al. Molecular analysis of common polymorphisms within the human Tyrosinase locus and genetic association with pigmentation traits. Pigment cell & melanoma research \n                           27, 552\u2013564, doi:10.1111\/pcmr.12253 (2014).","journal-title":"Pigment cell & melanoma research"},{"key":"4401_CR16","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.14977","author":"M Mondal","year":"2016","unstructured":"Mondal, M., Sengupta, M. & Ray, K. Functional assessment of tyrosinase variants identified in individuals with albinism is essential for unequivocal determination of genotype to phenotype correlation. Br. J. Dermatol.. doi:10.1111\/bjd.14977 (2016).","journal-title":"Br. J. Dermatol."},{"key":"4401_CR17","doi-asserted-by":"publisher","first-page":"1590","DOI":"10.1002\/ajmg.a.32939","volume":"149a","author":"PW Chiang","year":"2009","unstructured":"Chiang, P. W., Spector, E. & Tsai, A. C. Oculocutaneous albinism spectrum. Am. J. Med. Genet. A \n                           149a, 1590\u20131591, doi:10.1002\/ajmg.a.32939 (2009).","journal-title":"Am. J. Med. Genet. A"},{"key":"4401_CR18","first-page":"939","volume":"17","author":"MN Preising","year":"2011","unstructured":"Preising, M. N., Forster, H., Gonser, M. & Lorenz, B. Screening of TYR, OCA2, GPR143, and MC1R in patients with congenital nystagmus, macular hypoplasia, and fundus hypopigmentation indicating albinism. Mol. Vis. \n                           17, 939 (2011).","journal-title":"Mol. Vis."},{"key":"4401_CR19","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1038\/ng0195-92","volume":"9","author":"K Fukai","year":"1995","unstructured":"Fukai, K. et al. Autosomal recessive ocular albinism associated with a functionally significant tyrosinase gene polymorphism. Nat. Genet. \n                           9, 92\u201395 (1995).","journal-title":"Nat. Genet."},{"key":"4401_CR20","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1167\/iovs.07-0791","volume":"49","author":"SM Hutton","year":"2008","unstructured":"Hutton, S. M. & Spritz, R. A. A Comprehensive Genetic Study of Autosomal Recessive Ocular Albinism in Caucasian Patients. Invest. Ophthalmol. Vis. Sci. \n                           49, 868\u2013872, doi:10.1167\/iovs.07-0791 (2008b).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"4401_CR21","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1038\/nature15393","volume":"526","author":"A Auton","year":"2015","unstructured":"Auton, A. et al. A global reference for human genetic variation. Nature \n                           526, 68\u201374, doi:10.1038\/nature15393 (2015).","journal-title":"Nature"},{"key":"4401_CR22","first-page":"103","volume":"1","author":"RK Tripathi","year":"1991","unstructured":"Tripathi, R. K., Giebel, L. B., Strunk, K. M. & Spritz, R. A. A polymorphism of the human tyrosinase gene is associated with temperature-sensitive enzymatic activity. Gene Expr \n                           1, 103\u2013110 (1991).","journal-title":"Gene Expr"},{"key":"4401_CR23","doi-asserted-by":"publisher","first-page":"2149","DOI":"10.1096\/fj.01-0216com","volume":"15","author":"K Toyofuku","year":"2001","unstructured":"Toyofuku, K. et al. Oculocutaneous albinism types 1 and 3 are ER retention diseases: mutation of tyrosinase or Tyrp1 can affect the processing of both mutant and wild-type proteins. FASEB J. \n                           15, 2149\u20132161, doi:10.1096\/fj.01-0216com (2001).","journal-title":"FASEB J."},{"key":"4401_CR24","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1038\/jid.2010.274","volume":"131","author":"M Chaki","year":"2011","unstructured":"Chaki, M. et al. Molecular and functional studies of tyrosinase variants among Indian oculocutaneous albinism type 1 patients. J. Invest. Dermatol. \n                           131, 260\u2013262, doi:10.1038\/jid.2010.274 (2011).","journal-title":"J. Invest. Dermatol."},{"key":"4401_CR25","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1002\/ajmg.a.32654","volume":"149A","author":"WS Oetting","year":"2009","unstructured":"Oetting, W. S. et al. The R402Q tyrosinase variant does not cause autosomal recessive ocular albinism. American Journal of Medical Genetics Part A \n                           149A, 466\u2013469, doi:10.1002\/ajmg.a.32654 (2009).","journal-title":"American Journal of Medical Genetics Part A"},{"key":"4401_CR26","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1080\/07853890410026214","volume":"36","author":"ER Eichers","year":"2004","unstructured":"Eichers, E. R., Lewis, R. A., Katsanis, N. & Lupski, J. R. Triallelic inheritance: a bridge between Mendelian and multifactorial traits. Ann. Med. \n                           36, 262\u2013272 (2004).","journal-title":"Ann. Med."},{"key":"4401_CR27","doi-asserted-by":"publisher","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","volume":"25","author":"H Li","year":"2009","unstructured":"Li, H. et al. The Sequence Alignment\/Map format and SAMtools. Bioinformatics \n                           25, 2078\u20132079, doi:10.1093\/bioinformatics\/btp352 (2009).","journal-title":"Bioinformatics"},{"key":"4401_CR28","doi-asserted-by":"publisher","first-page":"e164","DOI":"10.1093\/nar\/gkq603","volume":"38","author":"K Wang","year":"2010","unstructured":"Wang, K., Li, M. & Hakonarson, H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res \n                           38, e164, doi:10.1093\/nar\/gkq603 (2010).","journal-title":"Nucleic Acids Res"},{"key":"4401_CR29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00439-013-1358-4","volume":"133","author":"PD Stenson","year":"2014","unstructured":"Stenson, P. D. et al. The Human Gene Mutation Database: building a comprehensive mutation repository for clinical and molecular genetics, diagnostic testing and personalized genomic medicine. Hum. Genet. \n                           133, 1\u20139, doi:10.1007\/s00439-013-1358-4 (2014).","journal-title":"Hum. Genet."},{"key":"4401_CR30","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1101\/gr.176601","volume":"11","author":"PC Ng","year":"2001","unstructured":"Ng, P. C. & Henikoff, S. Predicting Deleterious Amino Acid Substitutions. Genome Res. \n                           11, 863\u2013874, doi:10.1101\/gr.176601 (2001).","journal-title":"Genome Res."},{"key":"4401_CR31","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1038\/nmeth0410-248","volume":"7","author":"IA Adzhubei","year":"2010","unstructured":"Adzhubei, I. A. et al. A method and server for predicting damaging missense mutations. Nature methods \n                           7, 248\u2013249, doi:10.1038\/nmeth0410-248 (2010).","journal-title":"Nature methods"},{"key":"4401_CR32","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1038\/nmeth0410-250","volume":"7","author":"GM Cooper","year":"2010","unstructured":"Cooper, G. M. et al. Single-nucleotide evolutionary constraint scores highlight disease-causing mutations. Nature methods \n                           7, 250\u2013251, doi:10.1038\/nmeth0410-250 (2010).","journal-title":"Nature methods"},{"key":"4401_CR33","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1002\/humu.20171","volume":"26","author":"M Chaki","year":"2005","unstructured":"Chaki, M., Mukhopadhyay, A. & Ray, K. Determination of variants in the 3\u2019-region of the tyrosinase gene requires locus specific amplification. Hum. Mutat. \n                           26, 53\u201358, doi:10.1002\/humu.20171 (2005).","journal-title":"Hum. Mutat."},{"key":"4401_CR34","doi-asserted-by":"publisher","first-page":"e57","DOI":"10.1093\/nar\/gnf056","volume":"30","author":"JP Schouten","year":"2002","unstructured":"Schouten, J. P. et al. Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Res \n                           30, e57 (2002).","journal-title":"Nucleic Acids Res"},{"key":"4401_CR35","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1167\/iovs.08-2639","volume":"50","author":"K Gr\u00f8nskov","year":"2009","unstructured":"Gr\u00f8nskov, K. et al. Birth Prevalence and Mutation Spectrum in Danish Patients with Autosomal Recessive Albinism. Invest. Ophthalmol. Vis. Sci. \n                           50, 1058\u20131064, doi:10.1167\/iovs.08-2639 (2009).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"4401_CR36","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1016\/j.gene.2012.09.012","volume":"511","author":"M Mondal","year":"2012","unstructured":"Mondal, M., Sengupta, M., Samanta, S., Sil, A. & Ray, K. Molecular basis of albinism in India: evaluation of seven potential candidate genes and some new findings. Gene \n                           511, 470\u2013474, doi:10.1016\/j.gene.2012.09.012 (2012).","journal-title":"Gene"},{"key":"4401_CR37","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1002\/humu.9248","volume":"23","author":"S Opitz","year":"2004","unstructured":"Opitz, S., K\u00e4smann\u2010Kellner, B., Kaufmann, M., Schwinger, E. & Z\u00fchlke, C. Detection of 53 novel DNA variations within the tyrosinase gene and accumulation of mutations in 17 patients with albinism. Hum. Mutat. \n                           23, 630\u2013631 (2004).","journal-title":"Hum. Mutat."},{"key":"4401_CR38","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1034\/j.1600-0749.2003.00045.x","volume":"16","author":"WS Oetting","year":"2003","unstructured":"Oetting, W. S., Fryer, J. P., Shriram, S. & King, R. A. Oculocutaneous albinism type 1: the last 100 years. Pigment Cell Res \n                           16, 307\u2013311 (2003).","journal-title":"Pigment Cell Res"},{"key":"4401_CR39","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12546","author":"MB Dolinska","year":"2016","unstructured":"Dolinska, M. B. et al. Oculocutaneous Albinism Type 1: Link between Mutations, Tyrosinase Conformational Stability, and Enzymatic Activity. Pigment cell & melanoma research, doi:10.1111\/pcmr.12546 (2016).","journal-title":"Pigment cell & melanoma research"},{"key":"4401_CR40","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1111\/j.1755-148X.2008.00496.x","volume":"21","author":"C Rooryck","year":"2008","unstructured":"Rooryck, C. et al. Molecular diagnosis of oculocutaneous albinism: new mutations in the OCA1-4 genes and practical aspects. Pigment cell & melanoma research \n                           21, 583\u2013587, doi:10.1111\/j.1755-148X.2008.00496.x (2008).","journal-title":"Pigment cell & melanoma research"},{"key":"4401_CR41","first-page":"199","volume":"49","author":"WS Oetting","year":"1991","unstructured":"Oetting, W. S. et al. Three different frameshift mutations of the tyrosinase gene in type IA oculocutaneous albinism. Am. J. Hum. Genet. \n                           49, 199\u2013206 (1991).","journal-title":"Am. J. Hum. Genet."},{"key":"4401_CR42","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1002\/humu.9318","volume":"25","author":"WS Oetting","year":"2005","unstructured":"Oetting, W. S., Garrett, S. S., Brott, M. & King, R. A. P gene mutations associated with oculocutaneous albinism type II (OCA2). Hum. Mutat. \n                           25, 323, doi:10.1002\/humu.9318 (2005).","journal-title":"Hum. Mutat."},{"key":"4401_CR43","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1046\/j.1600-0749.2003.00099.x","volume":"16","author":"JP Fryer","year":"2003","unstructured":"Fryer, J. P., Oetting, W. S. & King, R. A. Identification and characterization of a DNase hypersensitive region of the human tyrosinase gene. Pigment Cell Res \n                           16, 679\u2013684 (2003).","journal-title":"Pigment Cell Res"},{"key":"4401_CR44","doi-asserted-by":"publisher","first-page":"3555","DOI":"10.1093\/bioinformatics\/btv402","volume":"31","author":"MJ Machiela","year":"2015","unstructured":"Machiela, M. J. & Chanock, S. J. LDlink: a web-based application for exploring population-specific haplotype structure and linking correlated alleles of possible functional variants. Bioinformatics \n                           31, 3555\u20133557, doi:10.1093\/bioinformatics\/btv402 (2015).","journal-title":"Bioinformatics"},{"key":"4401_CR45","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. \n                           17, 405\u2013423, doi:10.1038\/gim.2015.30 (2015).","journal-title":"Genet. Med."},{"key":"4401_CR46","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1111\/cge.12019","volume":"84","author":"T Kausar","year":"2013","unstructured":"Kausar, T., Bhatti, M., Ali, M., Shaikh, R. & Ahmed, Z. OCA5, a novel locus for non\u2010syndromic oculocutaneous albinism, maps to chromosome 4q24. Clin. Genet. \n                           84, 91\u201393 (2013).","journal-title":"Clin. Genet."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-04401-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-04401-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-04401-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T06:10:24Z","timestamp":1671775824000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-04401-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6,30]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["4401"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-04401-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6,30]]},"assertion":[{"value":"31 January 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 May 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 June 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"4415"}}