{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T23:55:38Z","timestamp":1793663738755,"version":"4.5.1"},"reference-count":17,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,1,24]],"date-time":"2019-01-24T00:00:00Z","timestamp":1548288000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,1,24]],"date-time":"2019-01-24T00:00:00Z","timestamp":1548288000000},"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>\n                  <jats:p>\n                    Oculocutaneous albinism (OCA) is a genetically heterogeneous disorder. Six genes are associated with autosomal recessive OCA (\n                    <jats:italic>TYR<\/jats:italic>\n                    ,\n                    <jats:italic>OCA2<\/jats:italic>\n                    ,\n                    <jats:italic>TYRP1<\/jats:italic>\n                    ,\n                    <jats:italic>SLC45A2<\/jats:italic>\n                    ,\n                    <jats:italic>SLC24A5<\/jats:italic>\n                    and\n                    <jats:italic>LRMDA<\/jats:italic>\n                    ), and one gene,\n                    <jats:italic>GPR143<\/jats:italic>\n                    , is associated with X-linked ocular albinism (OA). Molecular genetic analysis provides a genetic diagnosis in approximately 60% of individuals with clinical OA\/OCA. A considerably number of the remaining 40% are heterozygous for a causative sequence variation in\n                    <jats:italic>TYR<\/jats:italic>\n                    . To identify missing causative sequence variants in these, we used a NGS based approach, genotyping and segregation analysis. We report two putative pathogenic haplotypes which only differ by two extremely rare SNVs, indicating that the haplotypes have a common derivation. Both haplotypes segregate consistent with an autosomal recessive inheritance pattern and include the allele p.S192Y-p.R402Q. An explanation for the pathogenicity of the haplotypes could be the combination of p.S192Y and p.R402Q. Homozygosity for the pathogenic haplotypes causes a partial albinism phenotype. In our cohort, 15% of affected individuals had a molecular genetic diagnosis involving the pathogenic haplotype. Consequently, the prevalence of albinism seems to be substantially underestimated, and children with unexplained bilateral subnormal vision and\/or nystagmus should be analysed clinically and molecularly for albinism.\n                  <\/jats:p>","DOI":"10.1038\/s41598-018-37272-5","type":"journal-article","created":{"date-parts":[[2019,1,24]],"date-time":"2019-01-24T06:04:17Z","timestamp":1548309857000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["A pathogenic haplotype, common in Europeans, causes autosomal recessive albinism and uncovers missing heritability in OCA1"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2341-1326","authenticated-orcid":false,"given":"Karen","family":"Gr\u00f8nskov","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathrine","family":"Jespersgaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gitte Hoffmann","family":"Bruun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pernille","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Br\u00f8ndum-Nielsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7488-3035","authenticated-orcid":false,"given":"Brage S.","family":"Andresen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0095-8991","authenticated-orcid":false,"given":"Thomas","family":"Rosenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,1,24]]},"reference":[{"key":"37272_CR1","doi-asserted-by":"publisher","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 journal of rare diseases 2, 43 (2007).","journal-title":"Orphanet journal of rare diseases"},{"key":"37272_CR2","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 27, 11\u201318 (2014).","journal-title":"Pigment cell & melanoma research"},{"key":"37272_CR3","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1038\/nature23264","volume":"548","author":"L Maretty","year":"2017","unstructured":"Maretty, L. et al. Sequencing and de novo assembly of 150 genomes from denmark as a population reference. Nature 548, 87 (2017).","journal-title":"Nature"},{"key":"37272_CR4","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.ejps.2010.04.001","volume":"40","author":"E Mannermaa","year":"2010","unstructured":"Mannermaa, E. et al. 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