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Whole Exome Sequencing Reveals Clustering of Variants of Known Vitiligo Genes in Multiplex Consanguineous Pakistani Families

Vitiligo is an autoimmune complex pigmentation disease characterized by non-pigmented patches on the surface of the skin that affect approximately 0.5–2% population worldwide. The exact etiology is still unknown; however, vitiligo is hypothesized to be a multifactorial and genetically heterogeneous...

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Autores principales: Ishaq, Rafaqat, Ilyas, Muhammad, Habiba, Umme, Amin, Muhammad Noor ul, Saeed, Sadia, Raja, Ghazala Kaukab, Shaiq, Pakeeza Arzoo, Ahmed, Zubair M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10218579/
https://www.ncbi.nlm.nih.gov/pubmed/37239478
http://dx.doi.org/10.3390/genes14051118
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author Ishaq, Rafaqat
Ilyas, Muhammad
Habiba, Umme
Amin, Muhammad Noor ul
Saeed, Sadia
Raja, Ghazala Kaukab
Shaiq, Pakeeza Arzoo
Ahmed, Zubair M.
author_facet Ishaq, Rafaqat
Ilyas, Muhammad
Habiba, Umme
Amin, Muhammad Noor ul
Saeed, Sadia
Raja, Ghazala Kaukab
Shaiq, Pakeeza Arzoo
Ahmed, Zubair M.
author_sort Ishaq, Rafaqat
collection PubMed
description Vitiligo is an autoimmune complex pigmentation disease characterized by non-pigmented patches on the surface of the skin that affect approximately 0.5–2% 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>A), NRROS (c.197C>T) and HERC2 (c.10969G>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.
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spelling pubmed-102185792023-05-27 Whole Exome Sequencing Reveals Clustering of Variants of Known Vitiligo Genes in Multiplex Consanguineous Pakistani Families Ishaq, Rafaqat Ilyas, Muhammad Habiba, Umme Amin, Muhammad Noor ul Saeed, Sadia Raja, Ghazala Kaukab Shaiq, Pakeeza Arzoo Ahmed, Zubair M. Genes (Basel) Article Vitiligo is an autoimmune complex pigmentation disease characterized by non-pigmented patches on the surface of the skin that affect approximately 0.5–2% 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>A), NRROS (c.197C>T) and HERC2 (c.10969G>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. MDPI 2023-05-22 /pmc/articles/PMC10218579/ /pubmed/37239478 http://dx.doi.org/10.3390/genes14051118 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ishaq, Rafaqat
Ilyas, Muhammad
Habiba, Umme
Amin, Muhammad Noor ul
Saeed, Sadia
Raja, Ghazala Kaukab
Shaiq, Pakeeza Arzoo
Ahmed, Zubair M.
Whole Exome Sequencing Reveals Clustering of Variants of Known Vitiligo Genes in Multiplex Consanguineous Pakistani Families
title Whole Exome Sequencing Reveals Clustering of Variants of Known Vitiligo Genes in Multiplex Consanguineous Pakistani Families
title_full Whole Exome Sequencing Reveals Clustering of Variants of Known Vitiligo Genes in Multiplex Consanguineous Pakistani Families
title_fullStr Whole Exome Sequencing Reveals Clustering of Variants of Known Vitiligo Genes in Multiplex Consanguineous Pakistani Families
title_full_unstemmed Whole Exome Sequencing Reveals Clustering of Variants of Known Vitiligo Genes in Multiplex Consanguineous Pakistani Families
title_short Whole Exome Sequencing Reveals Clustering of Variants of Known Vitiligo Genes in Multiplex Consanguineous Pakistani Families
title_sort whole exome sequencing reveals clustering of variants of known vitiligo genes in multiplex consanguineous pakistani families
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10218579/
https://www.ncbi.nlm.nih.gov/pubmed/37239478
http://dx.doi.org/10.3390/genes14051118
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