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Genetic Causes of Oculocutaneous Albinism in Pakistani Population

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 autoso...

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Autores principales: Sajid, Zureesha, Yousaf, Sairah, Waryah, Yar M., Mughal, Tauqeer A., Kausar, Tasleem, Shahzad, Mohsin, Rao, Ali R., Abbasi, Ansar A., Shaikh, Rehan S., Waryah, Ali M., Riazuddin, Saima, Ahmed, Zubair M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066997/
https://www.ncbi.nlm.nih.gov/pubmed/33800529
http://dx.doi.org/10.3390/genes12040492
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author Sajid, Zureesha
Yousaf, Sairah
Waryah, Yar M.
Mughal, Tauqeer A.
Kausar, Tasleem
Shahzad, Mohsin
Rao, Ali R.
Abbasi, Ansar A.
Shaikh, Rehan S.
Waryah, Ali M.
Riazuddin, Saima
Ahmed, Zubair M.
author_facet Sajid, Zureesha
Yousaf, Sairah
Waryah, Yar M.
Mughal, Tauqeer A.
Kausar, Tasleem
Shahzad, Mohsin
Rao, Ali R.
Abbasi, Ansar A.
Shaikh, Rehan S.
Waryah, Ali M.
Riazuddin, Saima
Ahmed, Zubair M.
author_sort Sajid, Zureesha
collection PubMed
description 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.
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spelling pubmed-80669972021-04-25 Genetic Causes of Oculocutaneous Albinism in Pakistani Population Sajid, Zureesha Yousaf, Sairah Waryah, Yar M. Mughal, Tauqeer A. Kausar, Tasleem Shahzad, Mohsin Rao, Ali R. Abbasi, Ansar A. Shaikh, Rehan S. Waryah, Ali M. Riazuddin, Saima Ahmed, Zubair M. Genes (Basel) Article 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. MDPI 2021-03-28 /pmc/articles/PMC8066997/ /pubmed/33800529 http://dx.doi.org/10.3390/genes12040492 Text en © 2021 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 (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Sajid, Zureesha
Yousaf, Sairah
Waryah, Yar M.
Mughal, Tauqeer A.
Kausar, Tasleem
Shahzad, Mohsin
Rao, Ali R.
Abbasi, Ansar A.
Shaikh, Rehan S.
Waryah, Ali M.
Riazuddin, Saima
Ahmed, Zubair M.
Genetic Causes of Oculocutaneous Albinism in Pakistani Population
title Genetic Causes of Oculocutaneous Albinism in Pakistani Population
title_full Genetic Causes of Oculocutaneous Albinism in Pakistani Population
title_fullStr Genetic Causes of Oculocutaneous Albinism in Pakistani Population
title_full_unstemmed Genetic Causes of Oculocutaneous Albinism in Pakistani Population
title_short Genetic Causes of Oculocutaneous Albinism in Pakistani Population
title_sort genetic causes of oculocutaneous albinism in pakistani population
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066997/
https://www.ncbi.nlm.nih.gov/pubmed/33800529
http://dx.doi.org/10.3390/genes12040492
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