A Novel Missense Variant in Actin Binding Domain of MYH7 Is Associated With Left Ventricular Noncompaction
Cardiomyopathies are a group of common heart disorders that affect numerous people worldwide. Left ventricular non-compaction (LVNC) is a structural disorder of the ventricular wall, categorized as a type of cardiomyopathy that mostly caused by genetic disorders. Genetic variations are underlying ca...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2022.839862/full |
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| author | Mahdi Hesaraki Mahdi Hesaraki Ugur Bora Ugur Bora Sara Pahlavan Najmeh Salehi Najmeh Salehi Seyed Ahmad Mousavi Maryam Barekat Seyed Javad Rasouli Hossein Baharvand Hossein Baharvand Gunes Ozhan Gunes Ozhan Mehdi Totonchi Mehdi Totonchi Mehdi Totonchi |
| author_facet | Mahdi Hesaraki Mahdi Hesaraki Ugur Bora Ugur Bora Sara Pahlavan Najmeh Salehi Najmeh Salehi Seyed Ahmad Mousavi Maryam Barekat Seyed Javad Rasouli Hossein Baharvand Hossein Baharvand Gunes Ozhan Gunes Ozhan Mehdi Totonchi Mehdi Totonchi Mehdi Totonchi |
| author_sort | Mahdi Hesaraki |
| collection | DOAJ |
| description | Cardiomyopathies are a group of common heart disorders that affect numerous people worldwide. Left ventricular non-compaction (LVNC) is a structural disorder of the ventricular wall, categorized as a type of cardiomyopathy that mostly caused by genetic disorders. Genetic variations are underlying causes of developmental deformation of the heart wall and the resultant contractile insufficiency. Here, we investigated a family with several affected members exhibiting LVNC phenotype. By whole-exome sequencing (WES) of three affected members, we identified a novel heterozygous missense variant (c.1963C>A:p.Leu655Met) in the gene encoding myosin heavy chain 7 (MYH7). This gene is evolutionary conserved among different organisms. We identified MYH7 as a highly enriched myosin, compared to other types of myosin heavy chains, in skeletal and cardiac muscles. Furthermore, MYH7 was among a few classes of MYH in mouse heart that highly expresses from early embryonic to adult stages. In silico predictions showed an altered actin-myosin binding, resulting in weaker binding energy that can cause LVNC. Moreover, CRISPR/Cas9 mediated MYH7 knockout in zebrafish caused impaired cardiovascular development. Altogether, these findings provide the first evidence for involvement of p.Leu655Met missense variant in the incidence of LVNC, most probably through actin-myosin binding defects during ventricular wall morphogenesis. |
| first_indexed | 2024-12-14T06:00:39Z |
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| id | doaj.art-c96c0a1e523349b49c7abc909dac83bb |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-12-14T06:00:39Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-c96c0a1e523349b49c7abc909dac83bb2022-12-21T23:14:27ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-04-01910.3389/fcvm.2022.839862839862A Novel Missense Variant in Actin Binding Domain of MYH7 Is Associated With Left Ventricular NoncompactionMahdi Hesaraki0Mahdi Hesaraki1Ugur Bora2Ugur Bora3Sara Pahlavan4Najmeh Salehi5Najmeh Salehi6Seyed Ahmad Mousavi7Maryam Barekat8Seyed Javad Rasouli9Hossein Baharvand10Hossein Baharvand11Gunes Ozhan12Gunes Ozhan13Mehdi Totonchi14Mehdi Totonchi15Mehdi Totonchi16Department of Developmental Biology, School of Basic Sciences and Advanced Technologies in Biology, University of Science and Culture, Tehran, IranDepartment of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, IranIzmir Biomedicine and Genome Center (IBG), Dokuz Eylul University Health, Izmir, TurkeyIzmir International Biomedicine and Genome Institute (IBG-Izmir), Dokuz Eylul University, Izmir, TurkeyDepartment of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, IranDepartment of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, IranSchool of Biological Science, Institute for Research in Fundamental Sciences (IPM), Tehran, IranDepartment of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, IranDepartment of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, IranDepartment of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Münster, GermanyDepartment of Developmental Biology, School of Basic Sciences and Advanced Technologies in Biology, University of Science and Culture, Tehran, IranDepartment of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, IranIzmir Biomedicine and Genome Center (IBG), Dokuz Eylul University Health, Izmir, TurkeyIzmir International Biomedicine and Genome Institute (IBG-Izmir), Dokuz Eylul University, Izmir, TurkeyDepartment of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, IranDepartment of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, IranSchool of Biological Science, Institute for Research in Fundamental Sciences (IPM), Tehran, IranCardiomyopathies are a group of common heart disorders that affect numerous people worldwide. Left ventricular non-compaction (LVNC) is a structural disorder of the ventricular wall, categorized as a type of cardiomyopathy that mostly caused by genetic disorders. Genetic variations are underlying causes of developmental deformation of the heart wall and the resultant contractile insufficiency. Here, we investigated a family with several affected members exhibiting LVNC phenotype. By whole-exome sequencing (WES) of three affected members, we identified a novel heterozygous missense variant (c.1963C>A:p.Leu655Met) in the gene encoding myosin heavy chain 7 (MYH7). This gene is evolutionary conserved among different organisms. We identified MYH7 as a highly enriched myosin, compared to other types of myosin heavy chains, in skeletal and cardiac muscles. Furthermore, MYH7 was among a few classes of MYH in mouse heart that highly expresses from early embryonic to adult stages. In silico predictions showed an altered actin-myosin binding, resulting in weaker binding energy that can cause LVNC. Moreover, CRISPR/Cas9 mediated MYH7 knockout in zebrafish caused impaired cardiovascular development. Altogether, these findings provide the first evidence for involvement of p.Leu655Met missense variant in the incidence of LVNC, most probably through actin-myosin binding defects during ventricular wall morphogenesis.https://www.frontiersin.org/articles/10.3389/fcvm.2022.839862/fullcardiomyopathyLVNCWESmyosin heavy chain 7zebrafish |
| spellingShingle | Mahdi Hesaraki Mahdi Hesaraki Ugur Bora Ugur Bora Sara Pahlavan Najmeh Salehi Najmeh Salehi Seyed Ahmad Mousavi Maryam Barekat Seyed Javad Rasouli Hossein Baharvand Hossein Baharvand Gunes Ozhan Gunes Ozhan Mehdi Totonchi Mehdi Totonchi Mehdi Totonchi A Novel Missense Variant in Actin Binding Domain of MYH7 Is Associated With Left Ventricular Noncompaction Frontiers in Cardiovascular Medicine cardiomyopathy LVNC WES myosin heavy chain 7 zebrafish |
| title | A Novel Missense Variant in Actin Binding Domain of MYH7 Is Associated With Left Ventricular Noncompaction |
| title_full | A Novel Missense Variant in Actin Binding Domain of MYH7 Is Associated With Left Ventricular Noncompaction |
| title_fullStr | A Novel Missense Variant in Actin Binding Domain of MYH7 Is Associated With Left Ventricular Noncompaction |
| title_full_unstemmed | A Novel Missense Variant in Actin Binding Domain of MYH7 Is Associated With Left Ventricular Noncompaction |
| title_short | A Novel Missense Variant in Actin Binding Domain of MYH7 Is Associated With Left Ventricular Noncompaction |
| title_sort | novel missense variant in actin binding domain of myh7 is associated with left ventricular noncompaction |
| topic | cardiomyopathy LVNC WES myosin heavy chain 7 zebrafish |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2022.839862/full |
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