Novel ELN mutation in a Japanese family with a severe form of supravalvular aortic stenosis
Abstract Background Supravalvular aortic stenosis (SVAS) is one of the congenital cardiovascular diseases characterized by stenosis of the aorta. The stenotic lesions occur anywhere above the aortic valve in the aortic tree as well as pulmonary arteries and eventually leads to circulatory failure. T...
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| Format: | Article |
| Language: | English |
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Wiley
2019-11-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.986 |
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| author | Kaori Sugiyama Hitoshi Horigome Lisheng Lin Takashi Murakami Junko Shiono Yoshito Yamashiro Hiroyuki Matsuura Hitoshi Yoda Hiromi Yanagisawa |
| author_facet | Kaori Sugiyama Hitoshi Horigome Lisheng Lin Takashi Murakami Junko Shiono Yoshito Yamashiro Hiroyuki Matsuura Hitoshi Yoda Hiromi Yanagisawa |
| author_sort | Kaori Sugiyama |
| collection | DOAJ |
| description | Abstract Background Supravalvular aortic stenosis (SVAS) is one of the congenital cardiovascular diseases characterized by stenosis of the aorta. The stenotic lesions occur anywhere above the aortic valve in the aortic tree as well as pulmonary arteries and eventually leads to circulatory failure. The disease gene has been identified on the elastin gene (ELN) and two types of SVAS have been categorized; a familial type and an isolated type with the de novo mutation. Methods Fluorescent In situ hybridization (FISH) analysis and gene sequencing were performed in a two‐generation family in which severe form of SVAS was diagnosed. Results None of the patients tested showed microdeletion of ELN, LIMK1, and D7S613. A novel nonsense mutation of ELN (c.160G>T (p.(Gly54*)), RNA not analyzed) was found in exon 3 in three members; two of them died suddenly due to rapid progression of SVAS with possible arrhythmia in early infancy. A point mutation in the 5’ untranslated region, which was previously suggested to be associated with SVAS, did not co‐segregate with the SVAS phenotype and found to be SNPs. Conclusion Our report shows a broad spectrum of clinical features in family members sharing the identical mutations, suggesting a potential contribution of modifier gene(s) or interactions with environmental factors. |
| first_indexed | 2024-03-07T21:58:14Z |
| format | Article |
| id | doaj.art-8acfecc2d013401f941483ba06f60471 |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-03-07T21:58:14Z |
| publishDate | 2019-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-8acfecc2d013401f941483ba06f604712024-02-24T07:01:12ZengWileyMolecular Genetics & Genomic Medicine2324-92692019-11-01711n/an/a10.1002/mgg3.986Novel ELN mutation in a Japanese family with a severe form of supravalvular aortic stenosisKaori Sugiyama0Hitoshi Horigome1Lisheng Lin2Takashi Murakami3Junko Shiono4Yoshito Yamashiro5Hiroyuki Matsuura6Hitoshi Yoda7Hiromi Yanagisawa8Life Science Center for Survival Dynamics Tsukuba Advanced Research Alliance (TARA) University of Tsukuba Tsukuba JapanDepartment of Child Health Faculty of Medicine University of Tsukuba Tsukuba JapanDepartment of Pediatric Cardiology Ibaraki Children's Hospital Mito JapanDepartment of Child Health Faculty of Medicine University of Tsukuba Tsukuba JapanDepartment of Pediatric Cardiology Ibaraki Children's Hospital Mito JapanLife Science Center for Survival Dynamics Tsukuba Advanced Research Alliance (TARA) University of Tsukuba Tsukuba JapanDepartment of Pediatrics Toho University School of Medicine Tokyo JapanDepartment of Neonatology Toho University School of Medicine Tokyo JapanLife Science Center for Survival Dynamics Tsukuba Advanced Research Alliance (TARA) University of Tsukuba Tsukuba JapanAbstract Background Supravalvular aortic stenosis (SVAS) is one of the congenital cardiovascular diseases characterized by stenosis of the aorta. The stenotic lesions occur anywhere above the aortic valve in the aortic tree as well as pulmonary arteries and eventually leads to circulatory failure. The disease gene has been identified on the elastin gene (ELN) and two types of SVAS have been categorized; a familial type and an isolated type with the de novo mutation. Methods Fluorescent In situ hybridization (FISH) analysis and gene sequencing were performed in a two‐generation family in which severe form of SVAS was diagnosed. Results None of the patients tested showed microdeletion of ELN, LIMK1, and D7S613. A novel nonsense mutation of ELN (c.160G>T (p.(Gly54*)), RNA not analyzed) was found in exon 3 in three members; two of them died suddenly due to rapid progression of SVAS with possible arrhythmia in early infancy. A point mutation in the 5’ untranslated region, which was previously suggested to be associated with SVAS, did not co‐segregate with the SVAS phenotype and found to be SNPs. Conclusion Our report shows a broad spectrum of clinical features in family members sharing the identical mutations, suggesting a potential contribution of modifier gene(s) or interactions with environmental factors.https://doi.org/10.1002/mgg3.986ELNmodifier genepulmonary artery stenosissudden deathsupravalvular aortic stenosis |
| spellingShingle | Kaori Sugiyama Hitoshi Horigome Lisheng Lin Takashi Murakami Junko Shiono Yoshito Yamashiro Hiroyuki Matsuura Hitoshi Yoda Hiromi Yanagisawa Novel ELN mutation in a Japanese family with a severe form of supravalvular aortic stenosis Molecular Genetics & Genomic Medicine ELN modifier gene pulmonary artery stenosis sudden death supravalvular aortic stenosis |
| title | Novel ELN mutation in a Japanese family with a severe form of supravalvular aortic stenosis |
| title_full | Novel ELN mutation in a Japanese family with a severe form of supravalvular aortic stenosis |
| title_fullStr | Novel ELN mutation in a Japanese family with a severe form of supravalvular aortic stenosis |
| title_full_unstemmed | Novel ELN mutation in a Japanese family with a severe form of supravalvular aortic stenosis |
| title_short | Novel ELN mutation in a Japanese family with a severe form of supravalvular aortic stenosis |
| title_sort | novel eln mutation in a japanese family with a severe form of supravalvular aortic stenosis |
| topic | ELN modifier gene pulmonary artery stenosis sudden death supravalvular aortic stenosis |
| url | https://doi.org/10.1002/mgg3.986 |
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