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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...

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Autores principales: Sugiyama, Kaori, Horigome, Hitoshi, Lin, Lisheng, Murakami, Takashi, Shiono, Junko, Yamashiro, Yoshito, Matsuura, Hiroyuki, Yoda, Hitoshi, Yanagisawa, Hiromi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
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.
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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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