Reclassifying variations of unknown significance in diseases affecting Saudi Arabia’s population reveal new associations
Introduction: Physicians face diagnostic dilemmas upon reports indicating disease variants of unknown significance (VUS). The most puzzling cases are patients with rare diseases, where finding another matched genotype and phenotype to associate their results is challenging. This study aims to prove...
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| Format: | Article |
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Frontiers Media S.A.
2023-11-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1250317/full |
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| author | Mariam M. Al Eissa Mariam M. Al Eissa Raniah S. Alotibi Raniah S. Alotibi Bader Alhaddad Bader Alhaddad Taghrid Aloraini Taghrid Aloraini Manar S. Samman Abdulrahman AlAsiri Abdulrahman AlAsiri Mohamed Abouelhoda Amerh S. AlQahtani |
| author_facet | Mariam M. Al Eissa Mariam M. Al Eissa Raniah S. Alotibi Raniah S. Alotibi Bader Alhaddad Bader Alhaddad Taghrid Aloraini Taghrid Aloraini Manar S. Samman Abdulrahman AlAsiri Abdulrahman AlAsiri Mohamed Abouelhoda Amerh S. AlQahtani |
| author_sort | Mariam M. Al Eissa |
| collection | DOAJ |
| description | Introduction: Physicians face diagnostic dilemmas upon reports indicating disease variants of unknown significance (VUS). The most puzzling cases are patients with rare diseases, where finding another matched genotype and phenotype to associate their results is challenging. This study aims to prove the value of updating patient files with new classifications, potentially leading to better assessment and prevention.Methodology: We recruited retrospective phenotypic and genotypic data from King Saud Medical City, Riyadh, Kingdom of Saudi Arabia. Between September 2020 and December 2021, 1,080 patients’ genetic profiles were tested in a College of American Pathologists accredited laboratory. We excluded all confirmed pathogenic variants, likely pathogenic variants and copy number variations. Finally, we further reclassified 194 VUS using different local and global databases, employing in silico prediction to justify the phenotype–genotype association.Results: Of the 194 VUS, 90 remained VUS, and the other 104 were reclassified as follows: 16 pathogenic, 49 likely pathogenic, nine benign, and 30 likely benign. Moreover, most of these variants had never been observed in other local or international databases.Conclusion: Reclassifying the VUS adds value to understanding the causality of the phenotype if it has been reported in another family or population. The healthcare system should establish guidelines for re-evaluating VUS, and upgrading VUS should reflect on individual/family risks and management strategies. |
| first_indexed | 2024-03-11T14:12:22Z |
| format | Article |
| id | doaj.art-95ac75cb26ba4c4f8cf5594da067c504 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-03-11T14:12:22Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-95ac75cb26ba4c4f8cf5594da067c5042023-11-01T17:37:09ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-11-011410.3389/fgene.2023.12503171250317Reclassifying variations of unknown significance in diseases affecting Saudi Arabia’s population reveal new associationsMariam M. Al Eissa0Mariam M. Al Eissa1Raniah S. Alotibi2Raniah S. Alotibi3Bader Alhaddad4Bader Alhaddad5Taghrid Aloraini6Taghrid Aloraini7Manar S. Samman8Abdulrahman AlAsiri9Abdulrahman AlAsiri10Mohamed Abouelhoda11Amerh S. AlQahtani12Public Health Authority, Public Health Lab, Molecular Genetics Laboratory, Riyadh, Saudi ArabiaMedical School, AlFaisal University, Riyadh, Saudi ArabiaDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi ArabiaKing Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi ArabiaLaboratory Medicine Department, King Fahd University Hospital, Imam Abdulrahman Bin Faisal University, Dammam, Saudi ArabiaMolecular Genetics Department, King Saud Medical City, Riyadh, Saudi ArabiaDivision of Translational Pathology, Department of Laboratory Medicine, King Abdulaziz Medical City, Riyadh, Saudi ArabiaDepartment of Genetics, King Abdullah Specialized Children Hospital, King Abdulaziz Medical City, MNGHA, Riyadh, Saudi ArabiaDepartment of Pathology and Clinical Laboratory Medicine Administration, King Fahad Medical City (KFMC), Riyadh, Saudi Arabia0Medical Genomics Research Department, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia1Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, University of Utrecht, Utrecht, Netherlands2Chairman Computational Science Department at King Faisal Specialised Hospital and Research Center, KFSHRC, Riyadh, Saudi Arabia3Medical Genetics Department, King Saud Medical City, Riyadh, Saudi ArabiaIntroduction: Physicians face diagnostic dilemmas upon reports indicating disease variants of unknown significance (VUS). The most puzzling cases are patients with rare diseases, where finding another matched genotype and phenotype to associate their results is challenging. This study aims to prove the value of updating patient files with new classifications, potentially leading to better assessment and prevention.Methodology: We recruited retrospective phenotypic and genotypic data from King Saud Medical City, Riyadh, Kingdom of Saudi Arabia. Between September 2020 and December 2021, 1,080 patients’ genetic profiles were tested in a College of American Pathologists accredited laboratory. We excluded all confirmed pathogenic variants, likely pathogenic variants and copy number variations. Finally, we further reclassified 194 VUS using different local and global databases, employing in silico prediction to justify the phenotype–genotype association.Results: Of the 194 VUS, 90 remained VUS, and the other 104 were reclassified as follows: 16 pathogenic, 49 likely pathogenic, nine benign, and 30 likely benign. Moreover, most of these variants had never been observed in other local or international databases.Conclusion: Reclassifying the VUS adds value to understanding the causality of the phenotype if it has been reported in another family or population. The healthcare system should establish guidelines for re-evaluating VUS, and upgrading VUS should reflect on individual/family risks and management strategies.https://www.frontiersin.org/articles/10.3389/fgene.2023.1250317/fullsingle nucleotide variationvariants of unknown significanceexome sequencingnext-generation sequencingnovel variationdisease-related |
| spellingShingle | Mariam M. Al Eissa Mariam M. Al Eissa Raniah S. Alotibi Raniah S. Alotibi Bader Alhaddad Bader Alhaddad Taghrid Aloraini Taghrid Aloraini Manar S. Samman Abdulrahman AlAsiri Abdulrahman AlAsiri Mohamed Abouelhoda Amerh S. AlQahtani Reclassifying variations of unknown significance in diseases affecting Saudi Arabia’s population reveal new associations Frontiers in Genetics single nucleotide variation variants of unknown significance exome sequencing next-generation sequencing novel variation disease-related |
| title | Reclassifying variations of unknown significance in diseases affecting Saudi Arabia’s population reveal new associations |
| title_full | Reclassifying variations of unknown significance in diseases affecting Saudi Arabia’s population reveal new associations |
| title_fullStr | Reclassifying variations of unknown significance in diseases affecting Saudi Arabia’s population reveal new associations |
| title_full_unstemmed | Reclassifying variations of unknown significance in diseases affecting Saudi Arabia’s population reveal new associations |
| title_short | Reclassifying variations of unknown significance in diseases affecting Saudi Arabia’s population reveal new associations |
| title_sort | reclassifying variations of unknown significance in diseases affecting saudi arabia s population reveal new associations |
| topic | single nucleotide variation variants of unknown significance exome sequencing next-generation sequencing novel variation disease-related |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1250317/full |
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