Genetic evaluation of cardiomyopathies in Qatar identifies enrichment of pathogenic sarcomere gene variants and possible founder disease mutations in the Arabs
<h3>Background</h3><p dir="ltr">Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are serious inherited heart diseases with various causative mutations identified. The full spectrum of causative mutations remains to be discovered, especially in understudi...
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| مؤلفون آخرون: | , , , , , , , , |
| منشور في: |
2021
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| _version_ | 1864513517752680448 |
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| author | Kholoud N. Al‐Shafai (18459009) |
| author2 | Mohammed Al‐Hashemi (18459012) Chidambaram Manickam (18434100) Rania Musa (18459015) Senthil Selvaraj (314873) Najeeb Syed (12561967) Fazulur Vempalli (18459018) Muneera Ali (18459021) Magdi Yacoub (6893000) Xavier Estivill (23803) |
| author2_role | author author author author author author author author author |
| author_facet | Kholoud N. Al‐Shafai (18459009) Mohammed Al‐Hashemi (18459012) Chidambaram Manickam (18434100) Rania Musa (18459015) Senthil Selvaraj (314873) Najeeb Syed (12561967) Fazulur Vempalli (18459018) Muneera Ali (18459021) Magdi Yacoub (6893000) Xavier Estivill (23803) |
| author_role | author |
| dc.creator.none.fl_str_mv | Kholoud N. Al‐Shafai (18459009) Mohammed Al‐Hashemi (18459012) Chidambaram Manickam (18434100) Rania Musa (18459015) Senthil Selvaraj (314873) Najeeb Syed (12561967) Fazulur Vempalli (18459018) Muneera Ali (18459021) Magdi Yacoub (6893000) Xavier Estivill (23803) |
| dc.date.none.fl_str_mv | 2021-06-17T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1002/mgg3.1709 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Genetic_evaluation_of_cardiomyopathies_in_Qatar_identifies_enrichment_of_pathogenic_sarcomere_gene_variants_and_possible_founder_disease_mutations_in_the_Arabs/25712289 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Genetics Biomedical and clinical sciences Cardiovascular medicine and haematology cardiomyopathy targeted sequencing genetic variants Qatar |
| dc.title.none.fl_str_mv | Genetic evaluation of cardiomyopathies in Qatar identifies enrichment of pathogenic sarcomere gene variants and possible founder disease mutations in the Arabs |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <h3>Background</h3><p dir="ltr">Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are serious inherited heart diseases with various causative mutations identified. The full spectrum of causative mutations remains to be discovered, especially in understudied populations.</p><h3>Methods</h3><p dir="ltr">Here, we established the DOHA Registry and Biobank for cardiomyopathies in Qatar, followed by sequencing of 174 genes on 51 HCM and 53 DCM patients, and 31 relatives.</p><h3>Results</h3><p dir="ltr">In HCM, the analysis of 25 HCM‐associated genes showed that 20% of HCM cases had putative pathogenic variants for cardiomyopathy, mainly in sarcomere genes. Additional 49% of HCM cases had variants of uncertain significance, while 31% of HCM cases had likely benign variant(s) or had no variants identified within the analyzed HCM genes. In DCM, 56 putative DCM genes were analyzed. Eight percent of DCM cases had putative pathogenic variants for DCM, in the TTN gene while 70% of cases had variants of uncertain significance, in the analyzed DCM genes, that will need further pathogenicity assessment. Moreover, 22% of DCM cases remain unexplained, by having likely benign variant(s) or having no variants detected in any of the analyzed DCM genes.</p><h3>Conclusion</h3><p dir="ltr">We identified or replicated at least four recurrent variants among cardiomyopathy patients, which could be founder disease mutations in the Arabic population, including a frameshift variant (c.1371_1381dupTATCCAGTTAT) of unknown significance in the FKTN gene which seems to cause DCM in homozygosity, and HCM in heterozygosity. In vivo and/or in vitro functional validation need to be pursued in order to assess the pathogenicity of the identified variants.</p><h2>Other Information</h2><p dir="ltr">Published in: Molecular Genetics & Genomic Medicine<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1002/mgg3.1709" target="_blank">https://dx.doi.org/10.1002/mgg3.1709</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_9f7db4c9bdb02c209f803c7aacc5dee6 |
| identifier_str_mv | 10.1002/mgg3.1709 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25712289 |
| publishDate | 2021 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Genetic evaluation of cardiomyopathies in Qatar identifies enrichment of pathogenic sarcomere gene variants and possible founder disease mutations in the ArabsKholoud N. Al‐Shafai (18459009)Mohammed Al‐Hashemi (18459012)Chidambaram Manickam (18434100)Rania Musa (18459015)Senthil Selvaraj (314873)Najeeb Syed (12561967)Fazulur Vempalli (18459018)Muneera Ali (18459021)Magdi Yacoub (6893000)Xavier Estivill (23803)Biological sciencesGeneticsBiomedical and clinical sciencesCardiovascular medicine and haematologycardiomyopathytargeted sequencinggenetic variantsQatar<h3>Background</h3><p dir="ltr">Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are serious inherited heart diseases with various causative mutations identified. The full spectrum of causative mutations remains to be discovered, especially in understudied populations.</p><h3>Methods</h3><p dir="ltr">Here, we established the DOHA Registry and Biobank for cardiomyopathies in Qatar, followed by sequencing of 174 genes on 51 HCM and 53 DCM patients, and 31 relatives.</p><h3>Results</h3><p dir="ltr">In HCM, the analysis of 25 HCM‐associated genes showed that 20% of HCM cases had putative pathogenic variants for cardiomyopathy, mainly in sarcomere genes. Additional 49% of HCM cases had variants of uncertain significance, while 31% of HCM cases had likely benign variant(s) or had no variants identified within the analyzed HCM genes. In DCM, 56 putative DCM genes were analyzed. Eight percent of DCM cases had putative pathogenic variants for DCM, in the TTN gene while 70% of cases had variants of uncertain significance, in the analyzed DCM genes, that will need further pathogenicity assessment. Moreover, 22% of DCM cases remain unexplained, by having likely benign variant(s) or having no variants detected in any of the analyzed DCM genes.</p><h3>Conclusion</h3><p dir="ltr">We identified or replicated at least four recurrent variants among cardiomyopathy patients, which could be founder disease mutations in the Arabic population, including a frameshift variant (c.1371_1381dupTATCCAGTTAT) of unknown significance in the FKTN gene which seems to cause DCM in homozygosity, and HCM in heterozygosity. In vivo and/or in vitro functional validation need to be pursued in order to assess the pathogenicity of the identified variants.</p><h2>Other Information</h2><p dir="ltr">Published in: Molecular Genetics & Genomic Medicine<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1002/mgg3.1709" target="_blank">https://dx.doi.org/10.1002/mgg3.1709</a></p>2021-06-17T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1002/mgg3.1709https://figshare.com/articles/journal_contribution/Genetic_evaluation_of_cardiomyopathies_in_Qatar_identifies_enrichment_of_pathogenic_sarcomere_gene_variants_and_possible_founder_disease_mutations_in_the_Arabs/25712289CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/257122892021-06-17T03:00:00Z |
| spellingShingle | Genetic evaluation of cardiomyopathies in Qatar identifies enrichment of pathogenic sarcomere gene variants and possible founder disease mutations in the Arabs Kholoud N. Al‐Shafai (18459009) Biological sciences Genetics Biomedical and clinical sciences Cardiovascular medicine and haematology cardiomyopathy targeted sequencing genetic variants Qatar |
| status_str | publishedVersion |
| title | Genetic evaluation of cardiomyopathies in Qatar identifies enrichment of pathogenic sarcomere gene variants and possible founder disease mutations in the Arabs |
| title_full | Genetic evaluation of cardiomyopathies in Qatar identifies enrichment of pathogenic sarcomere gene variants and possible founder disease mutations in the Arabs |
| title_fullStr | Genetic evaluation of cardiomyopathies in Qatar identifies enrichment of pathogenic sarcomere gene variants and possible founder disease mutations in the Arabs |
| title_full_unstemmed | Genetic evaluation of cardiomyopathies in Qatar identifies enrichment of pathogenic sarcomere gene variants and possible founder disease mutations in the Arabs |
| title_short | Genetic evaluation of cardiomyopathies in Qatar identifies enrichment of pathogenic sarcomere gene variants and possible founder disease mutations in the Arabs |
| title_sort | Genetic evaluation of cardiomyopathies in Qatar identifies enrichment of pathogenic sarcomere gene variants and possible founder disease mutations in the Arabs |
| topic | Biological sciences Genetics Biomedical and clinical sciences Cardiovascular medicine and haematology cardiomyopathy targeted sequencing genetic variants Qatar |