A comprehensive genetic landscape of inherited retinal diseases in a large Pakistani cohort
Abstract Inherited retinal diseases (IRDs) are a group of rare Mendelian disorders that often result in progressive vision loss and potentially to complete blindness at the end stage. In this study, we investigated a large cohort of patients with IRDs from Pakistan, the world’s fifth most populous c...
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| Format: | Article |
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Nature Portfolio
2025-04-01
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| Series: | npj Genomic Medicine |
| Online Access: | https://doi.org/10.1038/s41525-025-00488-2 |
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| author | Mukhtar Ullah Atta Ur Rehman Mathieu Quinodoz Abdur Rashid Francesca Cancellieri Asad Munir Karolina Kaminska Afia Iqbal Samra Javed Muhammad Dawood Hafiz Muhammad Azhar Baig Shamim Saleha Shagufta Naz Humera Kausar Ali Muhammad Waryah Andrea Superti-Furga Muhammad Ansar Carlo Rivolta |
| author_facet | Mukhtar Ullah Atta Ur Rehman Mathieu Quinodoz Abdur Rashid Francesca Cancellieri Asad Munir Karolina Kaminska Afia Iqbal Samra Javed Muhammad Dawood Hafiz Muhammad Azhar Baig Shamim Saleha Shagufta Naz Humera Kausar Ali Muhammad Waryah Andrea Superti-Furga Muhammad Ansar Carlo Rivolta |
| author_sort | Mukhtar Ullah |
| collection | DOAJ |
| description | Abstract Inherited retinal diseases (IRDs) are a group of rare Mendelian disorders that often result in progressive vision loss and potentially to complete blindness at the end stage. In this study, we investigated a large cohort of patients with IRDs from Pakistan, the world’s fifth most populous country, which is also characterized by distinctive demographic features, such as a high prevalence of consanguinity, endogamy, and a wide variety of ethnic groups. Specifically, we examined a total of 213 unrelated families (722 affected individuals) from three very large geographical regions. We achieved precise molecular diagnosis in 171 pedigrees (80.3%) and detected causative variants in 60 different IRD-associated genes, revealing a mutational landscape that differed substantially from previous data from other European or Asian populations, heavily shaped by endogamy and rare or recurrent founder mutational events. To our knowledge, this work represents the largest genetic study on IRDs within the Pakistani population. |
| format | Article |
| id | doaj-art-aaed5f1003464c66bd8efd80994a9a34 |
| institution | OA Journals |
| issn | 2056-7944 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Genomic Medicine |
| spelling | doaj-art-aaed5f1003464c66bd8efd80994a9a342025-08-20T01:56:09ZengNature Portfolionpj Genomic Medicine2056-79442025-04-0110111110.1038/s41525-025-00488-2A comprehensive genetic landscape of inherited retinal diseases in a large Pakistani cohortMukhtar Ullah0Atta Ur Rehman1Mathieu Quinodoz2Abdur Rashid3Francesca Cancellieri4Asad Munir5Karolina Kaminska6Afia Iqbal7Samra Javed8Muhammad Dawood9Hafiz Muhammad Azhar Baig10Shamim Saleha11Shagufta Naz12Humera Kausar13Ali Muhammad Waryah14Andrea Superti-Furga15Muhammad Ansar16Carlo Rivolta17Ophthalmic Genetics, Institute of Molecular and Clinical Ophthalmology BaselDepartment of Zoology, Faculty of Biological and Health Sciences, Hazara UniversityOphthalmic Genetics, Institute of Molecular and Clinical Ophthalmology BaselDepartment of Zoology Islamia College University Peshawar, PeshawarOphthalmic Genetics, Institute of Molecular and Clinical Ophthalmology BaselDepartment of Zoology, Faculty of Biological and Health Sciences, Hazara UniversityOphthalmic Genetics, Institute of Molecular and Clinical Ophthalmology BaselDepartment of Zoology, Lahore College for Women UniversityDepartment of Biotechnology, Lahore College for Women UniversityDepartment of Biotechnology and Genetic Engineering, Kohat University of Science and TechnologyOphthalmic Genetics, Institute of Molecular and Clinical Ophthalmology BaselDepartment of Biotechnology and Genetic Engineering, Kohat University of Science and TechnologyDepartment of Zoology, Lahore College for Women UniversityDepartment of Biotechnology, Lahore College for Women UniversityDepartment of Molecular Biology and Genetics, Liaquat University of Medical and Health Sciences, JamshoroDivision of Genetic Medicine, University of LausanneDepartment of Ophthalmology, University of Lausanne, Jules Gonin Eye Hospital, Fondation Asile Des AveuglesOphthalmic Genetics, Institute of Molecular and Clinical Ophthalmology BaselAbstract Inherited retinal diseases (IRDs) are a group of rare Mendelian disorders that often result in progressive vision loss and potentially to complete blindness at the end stage. In this study, we investigated a large cohort of patients with IRDs from Pakistan, the world’s fifth most populous country, which is also characterized by distinctive demographic features, such as a high prevalence of consanguinity, endogamy, and a wide variety of ethnic groups. Specifically, we examined a total of 213 unrelated families (722 affected individuals) from three very large geographical regions. We achieved precise molecular diagnosis in 171 pedigrees (80.3%) and detected causative variants in 60 different IRD-associated genes, revealing a mutational landscape that differed substantially from previous data from other European or Asian populations, heavily shaped by endogamy and rare or recurrent founder mutational events. To our knowledge, this work represents the largest genetic study on IRDs within the Pakistani population.https://doi.org/10.1038/s41525-025-00488-2 |
| spellingShingle | Mukhtar Ullah Atta Ur Rehman Mathieu Quinodoz Abdur Rashid Francesca Cancellieri Asad Munir Karolina Kaminska Afia Iqbal Samra Javed Muhammad Dawood Hafiz Muhammad Azhar Baig Shamim Saleha Shagufta Naz Humera Kausar Ali Muhammad Waryah Andrea Superti-Furga Muhammad Ansar Carlo Rivolta A comprehensive genetic landscape of inherited retinal diseases in a large Pakistani cohort npj Genomic Medicine |
| title | A comprehensive genetic landscape of inherited retinal diseases in a large Pakistani cohort |
| title_full | A comprehensive genetic landscape of inherited retinal diseases in a large Pakistani cohort |
| title_fullStr | A comprehensive genetic landscape of inherited retinal diseases in a large Pakistani cohort |
| title_full_unstemmed | A comprehensive genetic landscape of inherited retinal diseases in a large Pakistani cohort |
| title_short | A comprehensive genetic landscape of inherited retinal diseases in a large Pakistani cohort |
| title_sort | comprehensive genetic landscape of inherited retinal diseases in a large pakistani cohort |
| url | https://doi.org/10.1038/s41525-025-00488-2 |
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