{"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":1776433171437,"version":"3.51.2"},"reference-count":35,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,3,28]],"date-time":"2021-03-28T00:00:00Z","timestamp":1616889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01AR077563"],"award-info":[{"award-number":["R01AR077563"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Melanin pigment helps protect our body from broad wavelength solar radiation and skin cancer. Among other pigmentation disorders in humans, albinism is reported to manifest in both syndromic and nonsyndromic forms as well as with varying inheritance patterns. Oculocutaneous albinism (OCA), an autosomal recessive nonsyndromic form of albinism, presents as partial to complete loss of melanin in the skin, hair, and iris. OCA has been known to be caused by pathogenic variants in seven different genes, so far, according to all the currently published population studies. However, the detection rate of alleles causing OCA varies from 50% to 90%. One of the significant challenges of uncovering the pathological variant underlying disease etiology is inter- and intra-familial locus heterogeneity. This problem is especially pertinent in highly inbred populations. As examples of such familial locus heterogeneity, we present nine consanguineous Pakistani families with segregating OCA due to variants in one or two different known albinism-associated genes. All of the identified variants are predicted to be pathogenic, which was corroborated by several in silico algorithms and association with diverse clinical phenotypes. We report an individual affected with OCA carries heterozygous, likely pathogenic variants in TYR and OCA2, raising the question of a possible digenic inheritance. Altogether, our study highlights the significance of exome sequencing for the complete genetic diagnosis of inbred families and provides the ramifications of potential genetic interaction and digenic inheritance of variants in the TYR and OCA2 genes.<\/jats:p>","DOI":"10.3390\/genes12040492","type":"journal-article","created":{"date-parts":[[2021,3,28]],"date-time":"2021-03-28T22:09:01Z","timestamp":1616969341000},"page":"492","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Genetic Causes of Oculocutaneous Albinism in Pakistani Population"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2337-5441","authenticated-orcid":false,"given":"Zureesha","family":"Sajid","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA"},{"name":"Institute of Molecular Biology and Biotechnology, Bahauddin Zakariya University, Multan 60000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sairah","family":"Yousaf","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yar M.","family":"Waryah","sequence":"additional","affiliation":[{"name":"Molecular Biology and Genetics Department, Liaquat University of Medical and Health Sciences, Jamshoro 76090, Pakistan"},{"name":"Department of Molecular Biology and Genetics, Shaheed Benazir Bhutto University, Shaheed Benazir Abad 67450, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tauqeer A.","family":"Mughal","sequence":"additional","affiliation":[{"name":"Department of Zoology, Mirpur University of Science and Technology, Mirpur, Azad Jammu and Kashmir 10250, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tasleem","family":"Kausar","sequence":"additional","affiliation":[{"name":"Department of Zoology, Government Sadiq College Women University, Bahawalpur 63100, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohsin","family":"Shahzad","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali R.","family":"Rao","sequence":"additional","affiliation":[{"name":"Molecular Biology and Genetics Department, Liaquat University of Medical and Health Sciences, Jamshoro 76090, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8140-0756","authenticated-orcid":false,"given":"Ansar A.","family":"Abbasi","sequence":"additional","affiliation":[{"name":"Department of Zoology, Mirpur University of Science and Technology, Mirpur, Azad Jammu and Kashmir 10250, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3648-6965","authenticated-orcid":false,"given":"Rehan S.","family":"Shaikh","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology, Bahauddin Zakariya University, Multan 60000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2596-9032","authenticated-orcid":false,"given":"Ali M.","family":"Waryah","sequence":"additional","affiliation":[{"name":"Molecular Biology and Genetics Department, Liaquat University of Medical and Health Sciences, Jamshoro 76090, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saima","family":"Riazuddin","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA"},{"name":"Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2914-4502","authenticated-orcid":false,"given":"Zubair M.","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA"},{"name":"Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3995","DOI":"10.1242\/jcs.040667","article-title":"Melanosomes at a glance","volume":"121","author":"Wasmeier","year":"2008","journal-title":"J. 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