Unveiling genetics of non-syndromic albinism using whole exome sequencing: A comprehensive study of TYR, TYRP1, OCA2 and MC1R genes in 17 families.

Autor: Zaman Q; Department of Zoology, Government Postgraduate College Dargai, Malakand 23050, Pakistan; Higher Education Department, Peshawar 25120, Government of Khyber Pakhtunkhwa, Pakistan; Department of Zoology, Abdul Wali Khan University, Mardan 23200, Pakistan., Khan J; Department of Zoology, Government Postgraduate College Dargai, Malakand 23050, Pakistan., Ahmad M; Department of Zoology, Government Postgraduate College Dargai, Malakand 23050, Pakistan., Khan H; Department of Zoology, Government Postgraduate College Dargai, Malakand 23050, Pakistan; Department of Zoology, Islamia College, Peshawar 25120, Pakistan., Chaudhary HT; Department of Pathology, Medical College, Taif University, Taif, Saudi Arabia., Rehman G; Department of Zoology, Abdul Wali Khan University, Mardan 23200, Pakistan., Rahman OU; Department of Biochemistry, Swat Medical College, Swat 19200, Pakistan., Shah MM; Department of Zoology, Government Postgraduate College Dargai, Malakand 23050, Pakistan., Hussain J; Department of Zoology, Government Postgraduate College Dargai, Malakand 23050, Pakistan., Jamal Q; Department of Zoology, University of Peshawar, Peshawar 25120, Pakistan., Khan BT; Department of Zoology, University of Peshawar, Peshawar 25120, Pakistan., Khan MA; Department of Zoology, Government Postgraduate College Dargai, Malakand 23050, Pakistan., Sadeeda; Department of Zoology, Government Postgraduate College Dargai, Malakand 23050, Pakistan., Sahar K; Department of Zoology, Government Postgraduate College Dargai, Malakand 23050, Pakistan., Idrees M; Department of Zoology, Government Postgraduate College Dargai, Malakand 23050, Pakistan., Ahmad R; Department of Zoology, Government Postgraduate College Timergara, Dir Lower 18300, Pakistan., Faisal MS; Department of Zoology, Islamia College, Peshawar 25120, Pakistan., Khan MI; Department of Zoology, Islamia College, Peshawar 25120, Pakistan., Khisroon M; Department of Zoology, University of Peshawar, Peshawar 25120, Pakistan., Abdulkareem AA; Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia; Faculty of Science, Department of Biochemistry, King Abdulaziz University, Jeddah, Saudi Arabia., Lee E; 3billion Inc., Seoul, Republic of Korea., Ryu SW; 3billion Inc., Seoul, Republic of Korea., Bibi N; Department of Bioinformatics, Shaheed Benazir Bhutto Women University, Peshawar 25120, Pakistan., Muthaffar OY; Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia., Jelani M; Rare Diseases Genetics and Genomics, Centre for Omic Sciences, Islamia College, Peshawar 25120, Pakistan. Electronic address: mjelani@icp.edu.pk., Naseer MI; Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia. Electronic address: minaseer@kau.edu.sa.
Jazyk: angličtina
Zdroj: Gene [Gene] 2024 Feb 05; Vol. 894, pp. 147986. Date of Electronic Publication: 2023 Nov 11.
DOI: 10.1016/j.gene.2023.147986
Abstrakt: Background: Oculocutaneous albinism (OCA) is a group of skin depigmentation disorders. Clinical presentation of OCA includes defects in melanocyte differentiation, melanin biosynthesis, and melanosome maturation and transport.
Objectives: A molecular diagnostics study of families presenting oculocutaneous albinism.
Methods: In this study, 17 consanguineous OCA families consisting of 93 patients were investigated. Whole Exome Sequencing (WES) of the index patient in each family were performed. Short listed variants of WES were Sanger validated for Mendelian segregation in obligate carriers and other available family members. Variant prioritization and pathogenicity were classified as per the criteria of American College Medical Genetics and Genomics (ACMG). Comparative computational modelling was performed to predict the potential damaging effect of the altered proteins.
Results: 15 pathogenic variations: c.132 T > A, c.346C > T, c.488C > G, c.1037G > A in TYR, c.1211C > T, c.1441G > A, c.1706_1707insT, c.2020C > G, c.2402G > C, c.2430del, in OCA2, c.1067G > A in TYRP1 and c.451C > T, c.515G > T, c.766C > T, c.917G > A in MC1R genes were identified. Three variants in OCA2 gene were characterized: c.1706_1707insT, c.2430del, and c.2402G > C, all of which were not reported before in OCA families.
Conclusion: A few studies focusing on mutation screening of OCA patients have been reported before; however, this study has uniquely presents the Pakhtun ethnic population residing on the North-Western boarder. It explains that TYR, OCA2, TYRP1, and MC1R variations lead to non-syndromic OCA phenotype The overlapping phenotypes of OCA can precisely be diagnosed for its molecular pathogenicity using WES. This study recommends WES as a first-line molecular diagnostic tool, and provides a basis for developing customized genetic tests i.e. pre-marital screening to reduce the disease burden in the future generations.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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