Identification and genetic analysis of rare variants in myosin family genes in 412 Han Chinese congenital heart disease patients
Abstract Background Myosin family genes, including those encoding myosin heavy chain 6, myosin heavy chain 7, myosin light chain 3, and myosin light chain 2 (MYL2), are important genetic factors in congenital heart disease (CHD). However, how these genes contribute to CHD in the Han Chinese populati...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-10-01
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| Series: | Molecular Genetics & Genomic Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mgg3.2041 |
| _version_ | 1828194351890563072 |
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| author | Yunqian Zhang Rui Peng Hongyan Wang |
| author_facet | Yunqian Zhang Rui Peng Hongyan Wang |
| author_sort | Yunqian Zhang |
| collection | DOAJ |
| description | Abstract Background Myosin family genes, including those encoding myosin heavy chain 6, myosin heavy chain 7, myosin light chain 3, and myosin light chain 2 (MYL2), are important genetic factors in congenital heart disease (CHD). However, how these genes contribute to CHD in the Han Chinese population remains unclear. Methods We sequenced myosin family genes in a Han Chinese cohort comprising 412 CHD patients and 213 matched controls in the present study. A zebrafish model was used to evaluate the pathogenicity of rare mutations in MYL2. Results We identified 30 known mutations and 12 novel mutations. Furthermore, the contributions of two novel mutations, MYL2 p.Ile158Thr and p.Val146Met, to CHD were analyzed. The p.Ile158Thr mutation increased MYL2 expression. In zebrafish embryos, injection of myl2b‐targeting morpholinos led to aberrant cardiac structures, an effect that was reversed by expression of wild‐type MYL2 but not MYL2 p.Ile158Thr and pVal146Met. Conclusions Overall, our findings suggest that MYL2 p.Ile158Thr and p.Val146Met contribute to the etiology of CHD. The results also indicate the importance of MYL2 in heart formation. |
| first_indexed | 2024-04-12T09:23:31Z |
| format | Article |
| id | doaj.art-6353cab6ac7c47e79ea3602d83240e28 |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-04-12T09:23:31Z |
| publishDate | 2022-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-6353cab6ac7c47e79ea3602d83240e282022-12-22T03:38:33ZengWileyMolecular Genetics & Genomic Medicine2324-92692022-10-011010n/an/a10.1002/mgg3.2041Identification and genetic analysis of rare variants in myosin family genes in 412 Han Chinese congenital heart disease patientsYunqian Zhang0Rui Peng1Hongyan Wang2Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, State Key Laboratory of Genetic Engineering at School of Life Sciences Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University Shanghai ChinaShanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, State Key Laboratory of Genetic Engineering at School of Life Sciences Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University Shanghai ChinaShanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, State Key Laboratory of Genetic Engineering at School of Life Sciences Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University Shanghai ChinaAbstract Background Myosin family genes, including those encoding myosin heavy chain 6, myosin heavy chain 7, myosin light chain 3, and myosin light chain 2 (MYL2), are important genetic factors in congenital heart disease (CHD). However, how these genes contribute to CHD in the Han Chinese population remains unclear. Methods We sequenced myosin family genes in a Han Chinese cohort comprising 412 CHD patients and 213 matched controls in the present study. A zebrafish model was used to evaluate the pathogenicity of rare mutations in MYL2. Results We identified 30 known mutations and 12 novel mutations. Furthermore, the contributions of two novel mutations, MYL2 p.Ile158Thr and p.Val146Met, to CHD were analyzed. The p.Ile158Thr mutation increased MYL2 expression. In zebrafish embryos, injection of myl2b‐targeting morpholinos led to aberrant cardiac structures, an effect that was reversed by expression of wild‐type MYL2 but not MYL2 p.Ile158Thr and pVal146Met. Conclusions Overall, our findings suggest that MYL2 p.Ile158Thr and p.Val146Met contribute to the etiology of CHD. The results also indicate the importance of MYL2 in heart formation.https://doi.org/10.1002/mgg3.2041congenital heart diseaseMYL2myosin familyrare variantszebrafish |
| spellingShingle | Yunqian Zhang Rui Peng Hongyan Wang Identification and genetic analysis of rare variants in myosin family genes in 412 Han Chinese congenital heart disease patients Molecular Genetics & Genomic Medicine congenital heart disease MYL2 myosin family rare variants zebrafish |
| title | Identification and genetic analysis of rare variants in myosin family genes in 412 Han Chinese congenital heart disease patients |
| title_full | Identification and genetic analysis of rare variants in myosin family genes in 412 Han Chinese congenital heart disease patients |
| title_fullStr | Identification and genetic analysis of rare variants in myosin family genes in 412 Han Chinese congenital heart disease patients |
| title_full_unstemmed | Identification and genetic analysis of rare variants in myosin family genes in 412 Han Chinese congenital heart disease patients |
| title_short | Identification and genetic analysis of rare variants in myosin family genes in 412 Han Chinese congenital heart disease patients |
| title_sort | identification and genetic analysis of rare variants in myosin family genes in 412 han chinese congenital heart disease patients |
| topic | congenital heart disease MYL2 myosin family rare variants zebrafish |
| url | https://doi.org/10.1002/mgg3.2041 |
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