{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T15:39:37Z","timestamp":1780760377994,"version":"3.54.1"},"reference-count":36,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,3,12]],"date-time":"2022-03-12T00:00:00Z","timestamp":1647043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009374","name":"Pakistan Science Foundation","doi-asserted-by":"publisher","award":["PSF\/Res\/P-UHS\/Med (492)"],"award-info":[{"award-number":["PSF\/Res\/P-UHS\/Med (492)"]}],"id":[{"id":"10.13039\/100009374","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Oculocutaneous albinism (OCA) is associated with a wide range of clinical presentations and has been categorized with syndromic and non-syndromic features. The most common causative genes in non-syndromic OCA are TYR and OCA2 and HSP1 is in the syndromic albinism. The objective of this study was to identify pathogenic variants in congenital OCA families from Pakistan. Eight consanguineous families were recruited, and clinical and ophthalmological examination was carried out to diagnose the disease. Whole blood was collected from the participating individuals, and genomic DNA was extracted for sequencing analysis. TruSight one-panel sequencing was carried out on one affected individual of each family, and termination Sanger sequencing was carried out to establish the co-segregation of the causative gene or genes. In silico analysis was conducted to predict the causative pathogenic variants. Two families were found to have novel genetic pathogenic variants, and six families harbored previously reported variants. One novel compound heterozygous pathogenic variant in the TYR gene, c.1002delA; p.Ala335LeufsTer20, a novel frameshift deletion pathogenic variant and c.832C&gt;T; and p.Arg278Ter (a known pathogenic variant) were found in one family, whereas HPS1; c.437G&gt;A; and p.Trp146Ter were detected in another family. The identification of new and previous pathogenic variants in TYR, OCA2, and HPS1 genes are causative of congenital OCA, and these findings are expanding the heterogeneity of OCA.<\/jats:p>","DOI":"10.3390\/genes13030503","type":"journal-article","created":{"date-parts":[[2022,3,13]],"date-time":"2022-03-13T22:29:43Z","timestamp":1647210583000},"page":"503","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Delineating Novel and Known Pathogenic Variants in TYR, OCA2 and HPS-1 Genes in Eight Oculocutaneous Albinism (OCA) Pakistani Families"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8228-346X","authenticated-orcid":false,"given":"Muhammad","family":"Shakil","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Health Sciences (UHS), Lahore 54600, Pakistan"},{"name":"Department of Biochemistry, King Edward Medical University, Lahore 54000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abida","family":"Akbar","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, International Islamic University, Islamabad 44000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazish Mahmood","family":"Aisha","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Services Institute of Medical Sciences, Lahore 54600, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Intzar","family":"Hussain","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Services, Institute of Medical Sciences, Lahore 54600, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9316-0967","authenticated-orcid":false,"given":"Muhammad Ikram","family":"Ullah","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 75471, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8921-4376","authenticated-orcid":false,"given":"Muhammad","family":"Atif","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 75471, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8257-4128","authenticated-orcid":false,"given":"Haiba","family":"Kaul","sequence":"additional","affiliation":[{"name":"Genetics Discipline, Department of Animal Breeding and Genetics, Faculty of Animal Production and Technology, Ravi Campus, University of Veterinary and Animal Sciences, Pattoki 55300, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3240-0741","authenticated-orcid":false,"given":"Ali","family":"Amar","sequence":"additional","affiliation":[{"name":"Department of Human Genetics and Molecular Biology, University of Health Sciences, Lahore 54600, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Zahid","family":"Latif","sequence":"additional","affiliation":[{"name":"Department of Community Medicine and Medical Education, Azra Naheed Medical College, The Superior University, Lahore 54600, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Atif","family":"Qureshi","sequence":"additional","affiliation":[{"name":"Department of Community Medicine and Medical Education, Azra Naheed Medical College, The Superior University, Lahore 54600, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saqib","family":"Mahmood","sequence":"additional","affiliation":[{"name":"Department of Human Genetics and Molecular Biology, University of Health Sciences, Lahore 54600, Pakistan"},{"name":"Institute of Biomedical & Allied Health Sciences, University of Health Sciences Lahore, Lahore 54600, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1038\/s41433-019-0436-9","article-title":"Tyrosinase (TYR) gene sequencing and literature review reveals recurrent pathogenic variants and multiple population founder gene pathogenic variants as causative of oculocutaneous albinism (OCA) in Pakistani families","volume":"33","author":"Shakil","year":"2019","journal-title":"Eye"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"44185","DOI":"10.1038\/srep44185","article-title":"Molecular outcomes, clinical consequences, and genetic diagnosis of Oculocutaneous Albinism in Pakistani population","volume":"7","author":"Shahzad","year":"2017","journal-title":"Sci. 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