Delineating Novel and Known Pathogenic Variants in <i>TYR</i>, <i>OCA2</i> and <i>HPS-1</i> Genes in Eight Oculocutaneous Albinism (OCA) Pakistani Families
Oculocutaneous albinism (OCA) is associated with a wide range of clinical presentations and has been categorized with syndromic and non-syndromic features. The most common causative genes in non-syndromic OCA are <i>TYR</i> and <i>OCA2</i> and <i>HSP1</i> is in th...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/13/3/503 |
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| author | Muhammad Shakil Abida Akbar Nazish Mahmood Aisha Intzar Hussain Muhammad Ikram Ullah Muhammad Atif Haiba Kaul Ali Amar Muhammad Zahid Latif Muhammad Atif Qureshi Saqib Mahmood |
| author_facet | Muhammad Shakil Abida Akbar Nazish Mahmood Aisha Intzar Hussain Muhammad Ikram Ullah Muhammad Atif Haiba Kaul Ali Amar Muhammad Zahid Latif Muhammad Atif Qureshi Saqib Mahmood |
| author_sort | Muhammad Shakil |
| collection | DOAJ |
| description | Oculocutaneous albinism (OCA) is associated with a wide range of clinical presentations and has been categorized with syndromic and non-syndromic features. The most common causative genes in non-syndromic OCA are <i>TYR</i> and <i>OCA2</i> and <i>HSP1</i> is in the syndromic albinism. The objective of this study was to identify pathogenic variants in congenital OCA families from Pakistan. Eight consanguineous families were recruited, and clinical and ophthalmological examination was carried out to diagnose the disease. Whole blood was collected from the participating individuals, and genomic DNA was extracted for sequencing analysis. TruSight one-panel sequencing was carried out on one affected individual of each family, and termination Sanger sequencing was carried out to establish the co-segregation of the causative gene or genes. In silico analysis was conducted to predict the causative pathogenic variants. Two families were found to have novel genetic pathogenic variants, and six families harbored previously reported variants. One novel compound heterozygous pathogenic variant in the <i>TYR</i> gene, c.1002delA; p.Ala335LeufsTer20, a novel frameshift deletion pathogenic variant and c.832C>T; and p.Arg278Ter (a known pathogenic variant) were found in one family, whereas <i>HPS1</i>; c.437G>A; and p.Trp146Ter were detected in another family. The identification of new and previous pathogenic variants in <i>TYR</i>, <i>OCA2</i>, and <i>HPS1</i> genes are causative of congenital OCA, and these findings are expanding the heterogeneity of OCA. |
| first_indexed | 2024-03-09T19:47:09Z |
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| id | doaj.art-47b3dc1b51bf48daa3c8cd058e2a01b5 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T19:47:09Z |
| publishDate | 2022-03-01 |
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| record_format | Article |
| series | Genes |
| spelling | doaj.art-47b3dc1b51bf48daa3c8cd058e2a01b52023-11-24T01:19:15ZengMDPI AGGenes2073-44252022-03-0113350310.3390/genes13030503Delineating Novel and Known Pathogenic Variants in <i>TYR</i>, <i>OCA2</i> and <i>HPS-1</i> Genes in Eight Oculocutaneous Albinism (OCA) Pakistani FamiliesMuhammad Shakil0Abida Akbar1Nazish Mahmood Aisha2Intzar Hussain3Muhammad Ikram Ullah4Muhammad Atif5Haiba Kaul6Ali Amar7Muhammad Zahid Latif8Muhammad Atif Qureshi9Saqib Mahmood10Department of Biochemistry, University of Health Sciences (UHS), Lahore 54600, PakistanDepartment of Biological Sciences, International Islamic University, Islamabad 44000, PakistanDepartment of Biochemistry, Services Institute of Medical Sciences, Lahore 54600, PakistanDepartment of Ophthalmology Services, Institute of Medical Sciences, Lahore 54600, PakistanDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 75471, Saudi ArabiaDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 75471, Saudi ArabiaGenetics Discipline, Department of Animal Breeding and Genetics, Faculty of Animal Production and Technology, Ravi Campus, University of Veterinary and Animal Sciences, Pattoki 55300, PakistanDepartment of Human Genetics and Molecular Biology, University of Health Sciences, Lahore 54600, PakistanDepartment of Community Medicine and Medical Education, Azra Naheed Medical College, The Superior University, Lahore 54600, PakistanDepartment of Community Medicine and Medical Education, Azra Naheed Medical College, The Superior University, Lahore 54600, PakistanDepartment of Human Genetics and Molecular Biology, University of Health Sciences, Lahore 54600, PakistanOculocutaneous albinism (OCA) is associated with a wide range of clinical presentations and has been categorized with syndromic and non-syndromic features. The most common causative genes in non-syndromic OCA are <i>TYR</i> and <i>OCA2</i> and <i>HSP1</i> is in the syndromic albinism. The objective of this study was to identify pathogenic variants in congenital OCA families from Pakistan. Eight consanguineous families were recruited, and clinical and ophthalmological examination was carried out to diagnose the disease. Whole blood was collected from the participating individuals, and genomic DNA was extracted for sequencing analysis. TruSight one-panel sequencing was carried out on one affected individual of each family, and termination Sanger sequencing was carried out to establish the co-segregation of the causative gene or genes. In silico analysis was conducted to predict the causative pathogenic variants. Two families were found to have novel genetic pathogenic variants, and six families harbored previously reported variants. One novel compound heterozygous pathogenic variant in the <i>TYR</i> gene, c.1002delA; p.Ala335LeufsTer20, a novel frameshift deletion pathogenic variant and c.832C>T; and p.Arg278Ter (a known pathogenic variant) were found in one family, whereas <i>HPS1</i>; c.437G>A; and p.Trp146Ter were detected in another family. The identification of new and previous pathogenic variants in <i>TYR</i>, <i>OCA2</i>, and <i>HPS1</i> genes are causative of congenital OCA, and these findings are expanding the heterogeneity of OCA.https://www.mdpi.com/2073-4425/13/3/503oculocutaneous albinism (OCA)Pakistani familiespathogenic variants<i>TYR</i><i>OCA2</i><i>HSP</i> |
| spellingShingle | Muhammad Shakil Abida Akbar Nazish Mahmood Aisha Intzar Hussain Muhammad Ikram Ullah Muhammad Atif Haiba Kaul Ali Amar Muhammad Zahid Latif Muhammad Atif Qureshi Saqib Mahmood Delineating Novel and Known Pathogenic Variants in <i>TYR</i>, <i>OCA2</i> and <i>HPS-1</i> Genes in Eight Oculocutaneous Albinism (OCA) Pakistani Families Genes oculocutaneous albinism (OCA) Pakistani families pathogenic variants <i>TYR</i> <i>OCA2</i> <i>HSP</i> |
| title | Delineating Novel and Known Pathogenic Variants in <i>TYR</i>, <i>OCA2</i> and <i>HPS-1</i> Genes in Eight Oculocutaneous Albinism (OCA) Pakistani Families |
| title_full | Delineating Novel and Known Pathogenic Variants in <i>TYR</i>, <i>OCA2</i> and <i>HPS-1</i> Genes in Eight Oculocutaneous Albinism (OCA) Pakistani Families |
| title_fullStr | Delineating Novel and Known Pathogenic Variants in <i>TYR</i>, <i>OCA2</i> and <i>HPS-1</i> Genes in Eight Oculocutaneous Albinism (OCA) Pakistani Families |
| title_full_unstemmed | Delineating Novel and Known Pathogenic Variants in <i>TYR</i>, <i>OCA2</i> and <i>HPS-1</i> Genes in Eight Oculocutaneous Albinism (OCA) Pakistani Families |
| title_short | Delineating Novel and Known Pathogenic Variants in <i>TYR</i>, <i>OCA2</i> and <i>HPS-1</i> Genes in Eight Oculocutaneous Albinism (OCA) Pakistani Families |
| title_sort | delineating novel and known pathogenic variants in i tyr i i oca2 i and i hps 1 i genes in eight oculocutaneous albinism oca pakistani families |
| topic | oculocutaneous albinism (OCA) Pakistani families pathogenic variants <i>TYR</i> <i>OCA2</i> <i>HSP</i> |
| url | https://www.mdpi.com/2073-4425/13/3/503 |
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