{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T13:39:32Z","timestamp":1776433172180,"version":"3.51.2"},"reference-count":18,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,3,13]],"date-time":"2019-03-13T00:00:00Z","timestamp":1552435200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004681","name":"Higher Education Commission, Pakistan","doi-asserted-by":"publisher","award":["IRSIP."],"award-info":[{"award-number":["IRSIP."]}],"id":[{"id":"10.13039\/501100004681","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Human Genetics"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Oculocutaneous albinism (OCA) is an autosomal\u2010recessive disorder of a defective melanin pathway. The condition is characterized by hypopigmentation of hair, dermis, and ocular tissue. Genetic studies have reported seven nonsyndromic OCA genes, among which Pakistani OCA families mostly segregate <jats:italic>TYR<\/jats:italic> and <jats:italic>OCA2<\/jats:italic> gene mutations. Here in the present study, we investigate the genetic factors of eight consanguineous OCA families from Pakistan. Genetic analysis was performed through single\u2010nucleotide polymorphism (SNP) genotyping (for homozygosity mapping), whole exome sequencing (for mutation identification), Sanger sequencing (for validation and segregation analysis), and quantitative PCR (qPCR) (for copy number variant [CNV] validation). Genetic mapping in one family identified a novel homozygous deletion mutation of the entire <jats:italic>TYRP1<\/jats:italic> gene, and a novel deletion of exon 19 in the <jats:italic>OCA2<\/jats:italic> gene in two apparently unrelated families. In three further families, we identified homozygous mutations in <jats:italic>TYR<\/jats:italic> (NM_000372.4:c.1424G\u00a0&gt;\u00a0A; p.Trp475*), NM_000372.4:c.895C\u00a0&gt;\u00a0T; p.Arg299Cys), and <jats:italic>SLC45A2<\/jats:italic> (NM_016180:c.1532C\u00a0&gt;\u00a0T; p.Ala511Val). For the remaining two families, G and H, compound heterozygous <jats:italic>TYR<\/jats:italic> variants NM_000372.4:c.1037\u20107T\u00a0&gt;\u00a0A, NM_000372.4:c.1255G\u00a0&gt;\u00a0A (p.Gly419Arg), and NM_000372.4:c.1255G\u00a0&gt;\u00a0A (p.Gly419Arg) and novel variant NM_000372.4:c.248T\u00a0&gt;\u00a0G; (p.Val83Gly), respectively, were found. Our study further extends the evidence of <jats:italic>TYR<\/jats:italic> and <jats:italic>OCA2<\/jats:italic> as genetic mutation hot spots in Pakistani families. Genetic screening of additional OCA cases may also contribute toward the development of Pakistani specific molecular diagnostic tests, genetic counseling, and personalized healthcare.<\/jats:p>","DOI":"10.1111\/ahg.12307","type":"journal-article","created":{"date-parts":[[2019,3,14]],"date-time":"2019-03-14T01:50:51Z","timestamp":1552528251000},"page":"278-284","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Genetic studies of multiple consanguineous Pakistani families segregating oculocutaneous albinism identified novel and reported mutations"],"prefix":"10.1111","volume":"83","author":[{"given":"Hadia","family":"Gul","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Faculty of Sciences Gomal University  D.I. Khan Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdul Haleem","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Faculty of Sciences Gomal University  D.I. Khan Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo","family":"Harripaul","sequence":"additional","affiliation":[{"name":"Molecular Neuro\u2010Psychiatry and Development Lab (MiND), Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health University of Toronto  Toronto Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Mikhailov","sequence":"additional","affiliation":[{"name":"Molecular Neuro\u2010Psychiatry and Development Lab (MiND), Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health University of Toronto  Toronto Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamalben","family":"Prajapati","sequence":"additional","affiliation":[{"name":"Molecular Neuro\u2010Psychiatry and Development Lab (MiND), Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health University of Toronto  Toronto Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0085-4298","authenticated-orcid":false,"given":"Ejazullah","family":"Khan","sequence":"additional","affiliation":[{"name":"Gomal Centre of Biochemistry and Biotechnology Gomal University  D.I. Khan Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farman","family":"Ullah","sequence":"additional","affiliation":[{"name":"Gomal Centre of Biochemistry and Biotechnology Gomal University  D.I. Khan Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad","family":"Zubair","sequence":"additional","affiliation":[{"name":"Gomal Centre of Biochemistry and Biotechnology Gomal University  D.I. Khan Pakistan"},{"name":"Department of Cell and Developmental Biology, School of Life Sciences University of Science and Technology  Hefei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad Zeeshan","family":"Ali","sequence":"additional","affiliation":[{"name":"Gomal Centre of Biochemistry and Biotechnology Gomal University  D.I. Khan Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayesha Haleem","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Faculty of Sciences Gomal University  D.I. Khan Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Said","family":"Salman","sequence":"additional","affiliation":[{"name":"Department of Plant Breeding and Genetics Ghazi University  D.G. Khan Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5037-1473","authenticated-orcid":false,"given":"Saadullah","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering Kohat University of Science and Technology  Kohat Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John B.","family":"Vincent","sequence":"additional","affiliation":[{"name":"Molecular Neuro\u2010Psychiatry and Development Lab (MiND), Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health University of Toronto  Toronto Canada"},{"name":"Department of Psychiatry University of Toronto  Toronto Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8591-0377","authenticated-orcid":false,"given":"Muzammil Ahmad","family":"Khan","sequence":"additional","affiliation":[{"name":"Gomal Centre of Biochemistry and Biotechnology Gomal University  D.I. Khan Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,3,13]]},"reference":[{"key":"e_1_2_14_2_1","first-page":"1145","article-title":"Mutations in and lack of expression of tyrosinase\u2010related protein\u20101 (TRP\u20101) in melanocytes from an individual with brown oculocutaneous albinism: A new subtype of albinism classified as \u201cOCA3","volume":"58","author":"Boissy R. E.","year":"1996","journal-title":"American Journal of Human Genetics"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2005.00460.x"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu149"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2004.06.007"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-2-43"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.08-2639"},{"key":"e_1_2_14_8_1","first-page":"790","article-title":"Ophthalmo\u2010genetic analysis of Pakistani patients with nonsyndromic oculocutaneous albinism through whole exome sequencing","volume":"67","author":"Gul H.","year":"2017","journal-title":"JPMA. The Journal of the Pakistan Medical Association"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2012.432"},{"key":"e_1_2_14_10_1","first-page":"33","article-title":"Medico\u2010genetics of oculocutaneous albinism; an updated study with Pakistani perspective","volume":"54","author":"Khan M. A.","year":"2015","journal-title":"Pakistan Journal of Medical Research"},{"issue":"1","key":"e_1_2_14_11_1","first-page":"19","article-title":"Non\u2010random distribution of missense mutations within the human tyrosinase gene in type I (tyrosinase\u2010related) oculocutaneous albinism","volume":"8","author":"King R. A.","year":"1991","journal-title":"Molecular Biology & Medicine"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-003-0998-1"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1086\/301603"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0749.2006.00298.x"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp369"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep44185"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2008.07.002"}],"container-title":["Annals of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fahg.12307","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ahg.12307","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ahg.12307","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ahg.12307","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T16:21:00Z","timestamp":1693412460000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ahg.12307"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,13]]},"references-count":18,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,7]]}},"alternative-id":["10.1111\/ahg.12307"],"URL":"https:\/\/doi.org\/10.1111\/ahg.12307","archive":["Portico"],"relation":{},"ISSN":["0003-4800","1469-1809"],"issn-type":[{"value":"0003-4800","type":"print"},{"value":"1469-1809","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,13]]},"assertion":[{"value":"2018-08-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-02-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}