{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T17:42:32Z","timestamp":1785519752892,"version":"3.56.0"},"reference-count":26,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T00:00:00Z","timestamp":1684713600000},"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 Disease","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>Vitiligo is an autoimmune complex pigmentation disease characterized by non-pigmented patches on the surface of the skin that affect approximately 0.5\u20132% population worldwide. The exact etiology is still unknown; however, vitiligo is hypothesized to be a multifactorial and genetically heterogeneous condition. Therefore, the current study is designed to investigate the anthropometric presentation and genetic spectrum of vitiligo in fifteen consanguineous Pakistani families. The clinical evaluation of participating individuals revealed varying degrees of disease severity, with 23 years as the average age of disease onset. The majority of the affected individuals had non-segmental vitiligo (NSV). Whole exome sequencing analysis revealed clustering of rare variants of known vitiligo-associated genes. For instance, in the affected individuals of family VF-12, we identified three novel rare variants of PTPN22 (c.1108C&gt;A), NRROS (c.197C&gt;T) and HERC2 (c.10969G&gt;A) genes. All three variants replaced evolutionarily conserved amino acid residues in encoded proteins, which are predicted to impact the ionic interactions in the secondary structure. Although various in silico algorithms predicted low effect sizes for these variants individually, the clustering of them in affected individuals increases the polygenic burden of risk alleles. To our knowledge, this is the first study that highlights the complex etiology of vitiligo and genetic heterogeneity in multiplex consanguineous Pakistani families.<\/jats:p>","DOI":"10.3390\/genes14051118","type":"journal-article","created":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T02:28:42Z","timestamp":1684722522000},"page":"1118","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Whole Exome Sequencing Reveals Clustering of Variants of Known Vitiligo Genes in Multiplex Consanguineous Pakistani Families"],"prefix":"10.3390","volume":"14","author":[{"given":"Rafaqat","family":"Ishaq","sequence":"first","affiliation":[{"name":"University Institute of Biochemistry and Biotechnology, Pir Mehr Ali Shah Arid Agriculture University, Rawalpindi 46300, Pakistan"},{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, University of Maryland, Baltimore, MD 20742, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2168-8652","authenticated-orcid":false,"given":"Muhammad","family":"Ilyas","sequence":"additional","affiliation":[{"name":"University Institute of Biochemistry and Biotechnology, Pir Mehr Ali Shah Arid Agriculture University, Rawalpindi 46300, Pakistan"},{"name":"Department of Medical Laboratory Technology, Riphah International University, Malakand Campus, Malakand 23010, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umme","family":"Habiba","sequence":"additional","affiliation":[{"name":"University Institute of Biochemistry and Biotechnology, Pir Mehr Ali Shah Arid Agriculture University, Rawalpindi 46300, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Noor ul","family":"Amin","sequence":"additional","affiliation":[{"name":"University Institute of Biochemistry and Biotechnology, Pir Mehr Ali Shah Arid Agriculture University, Rawalpindi 46300, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6587-6543","authenticated-orcid":false,"given":"Sadia","family":"Saeed","sequence":"additional","affiliation":[{"name":"University Institute of Biochemistry and Biotechnology, Pir Mehr Ali Shah Arid Agriculture University, Rawalpindi 46300, Pakistan"},{"name":"Department of Clinical Molecular Biology, EpiGen, Institute of Clinical Medicine, University of Oslo, 0313 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8362-7137","authenticated-orcid":false,"given":"Ghazala Kaukab","family":"Raja","sequence":"additional","affiliation":[{"name":"University Institute of Biochemistry and Biotechnology, Pir Mehr Ali Shah Arid Agriculture University, Rawalpindi 46300, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0952-5375","authenticated-orcid":false,"given":"Pakeeza Arzoo","family":"Shaiq","sequence":"additional","affiliation":[{"name":"University Institute of Biochemistry and Biotechnology, Pir Mehr Ali Shah Arid Agriculture University, Rawalpindi 46300, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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, School of Medicine, University of Maryland, Baltimore, MD 20742, USA"},{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, MD 20742, USA"},{"name":"Department of Ophthalmology and Visual Sciences, School of Medicine, University of Maryland, Baltimore, MD 20742, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1159\/000506103","article-title":"Vitiligo: A Review","volume":"236","author":"Berqvist","year":"2020","journal-title":"Dermatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.3892\/etm.2014.1975","article-title":"Protein tyrosine phosphatase PTPN22 +1858C\/T polymorphism is associated with active vitiligo","volume":"8","year":"2014","journal-title":"Exp. 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