Unveiling genetics of non-syndromic albinism using whole exome sequencing : A comprehensive study of TYR, TYRP1, OCA2 and MC1R genes in 17 families
Copyright © 2023 Elsevier B.V. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:894 |
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| Enthalten in: |
Gene - 894(2024) vom: 05. Jan., Seite 147986 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zaman, Qaiser [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 01.01.2024 Date Revised 01.01.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.gene.2023.147986 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Zaman, Qaiser |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Unveiling genetics of non-syndromic albinism using whole exome sequencing |b A comprehensive study of TYR, TYRP1, OCA2 and MC1R genes in 17 families |
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| 500 | |a Date Completed 01.01.2024 | ||
| 500 | |a Date Revised 01.01.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 Elsevier B.V. All rights reserved. | ||
| 520 | |a 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 | ||
| 520 | |a OBJECTIVES: A molecular diagnostics study of families presenting oculocutaneous albinism | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Melanocytes | |
| 650 | 4 | |a Molecular diagnostics | |
| 650 | 4 | |a Oculocutaneous albinism | |
| 650 | 4 | |a Skin depigmentation | |
| 650 | 4 | |a Whole exome sequencing | |
| 650 | 7 | |a OCA2 protein, human |2 NLM | |
| 650 | 7 | |a Membrane Transport Proteins |2 NLM | |
| 650 | 7 | |a TYRP1 protein, human |2 NLM | |
| 650 | 7 | |a EC 1.14.18.- |2 NLM | |
| 650 | 7 | |a Membrane Glycoproteins |2 NLM | |
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