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Novel ELN mutation in a Japanese family with a severe form of supravalvular aortic stenosis
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 disea...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825854/ https://www.ncbi.nlm.nih.gov/pubmed/31560829 http://dx.doi.org/10.1002/mgg3.986 |
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author | Sugiyama, Kaori Horigome, Hitoshi Lin, Lisheng Murakami, Takashi Shiono, Junko Yamashiro, Yoshito Matsuura, Hiroyuki Yoda, Hitoshi Yanagisawa, Hiromi |
author_facet | Sugiyama, Kaori Horigome, Hitoshi Lin, Lisheng Murakami, Takashi Shiono, Junko Yamashiro, Yoshito Matsuura, Hiroyuki Yoda, Hitoshi Yanagisawa, Hiromi |
author_sort | Sugiyama, Kaori |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6825854 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-68258542019-11-07 Novel ELN mutation in a Japanese family with a severe form of supravalvular aortic stenosis Sugiyama, Kaori Horigome, Hitoshi Lin, Lisheng Murakami, Takashi Shiono, Junko Yamashiro, Yoshito Matsuura, Hiroyuki Yoda, Hitoshi Yanagisawa, Hiromi Mol Genet Genomic Med Clinical Report 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. John Wiley and Sons Inc. 2019-09-27 /pmc/articles/PMC6825854/ /pubmed/31560829 http://dx.doi.org/10.1002/mgg3.986 Text en © 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Clinical Report Sugiyama, Kaori Horigome, Hitoshi Lin, Lisheng Murakami, Takashi Shiono, Junko Yamashiro, Yoshito Matsuura, Hiroyuki Yoda, Hitoshi Yanagisawa, Hiromi Novel ELN mutation in a Japanese family with a severe form of 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 | Clinical Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825854/ https://www.ncbi.nlm.nih.gov/pubmed/31560829 http://dx.doi.org/10.1002/mgg3.986 |
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