Identification and characterization of a novel ELN mutation in congenital heart disease with pulmonary artery stenosis

Abstract Congenital heart defects, one of the most common birth defects, affect approximately 1% of live birth globally and remain the leading cause of infant mortality in developed countries. Utilizing the pathogenicity score and inheritance mode from whole exome sequencing results, a heterozygous...

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Autores principales:	Cuilan Hou, Junmin Zheng, Wei liu, Lijian Xie, Xiaomin Sun, Yongwei Zhang, Meng Xu, Yun Li, Tingting Xiao
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/466dd8c586fc48849f1138dc511088cb
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spelling	oai:doaj.org-article:466dd8c586fc48849f1138dc511088cb2021-12-02T18:34:13ZIdentification and characterization of a novel ELN mutation in congenital heart disease with pulmonary artery stenosis10.1038/s41598-021-93736-12045-2322https://doaj.org/article/466dd8c586fc48849f1138dc511088cb2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93736-1https://doaj.org/toc/2045-2322Abstract Congenital heart defects, one of the most common birth defects, affect approximately 1% of live birth globally and remain the leading cause of infant mortality in developed countries. Utilizing the pathogenicity score and inheritance mode from whole exome sequencing results, a heterozygous mutation (NM_001278939.1: c.1939G>T, p.Gly647Ter) in elastin (ELN) was identified among 6,440 variants in a female proband born with an atrial septal defect accompanied by pulmonary artery stenosis. Results of RT-PCR showed that the mutation (NM_001278939.1: c.1939G>T, p.Gly647Ter) did not affect the expression levels of ELN mRNA but increased protein level. The content of ELN truncate (functional component) was significantly lower in both the intracellular and extracellular compartments after mutation. These results indicate that the ELN mutation (NM_001278939.1: c.1939G>T, p.Gly647Ter) affected the protein truncate, which may be a functional component of ELN and play crucial roles for this pedigree. Here we report of an ELN heterozygous variant associated with congenital heart disease accompanied with pulmonary artery stenosis, which is less common. Based on our results, we speculate that this may be the main molecular mechanism underlying the mutation-led functional changes, and propose that the decrease of ELN protein level may cause this pedigree vascular abnormality, especially pulmonary artery stenosis, and reinforce the view that ELN insufficiency is the primary cause of these vascular lesions. This may be the main molecular mechanism underlying the mutation-led functional changes. Thus, systematic analysis not only enables us to better understand the etiology of this disease but also contributes to clinical and prenatal diagnosis.Cuilan HouJunmin ZhengWei liuLijian XieXiaomin SunYongwei ZhangMeng XuYun LiTingting XiaoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Cuilan Hou Junmin Zheng Wei liu Lijian Xie Xiaomin Sun Yongwei Zhang Meng Xu Yun Li Tingting Xiao Identification and characterization of a novel ELN mutation in congenital heart disease with pulmonary artery stenosis
description	Abstract Congenital heart defects, one of the most common birth defects, affect approximately 1% of live birth globally and remain the leading cause of infant mortality in developed countries. Utilizing the pathogenicity score and inheritance mode from whole exome sequencing results, a heterozygous mutation (NM_001278939.1: c.1939G>T, p.Gly647Ter) in elastin (ELN) was identified among 6,440 variants in a female proband born with an atrial septal defect accompanied by pulmonary artery stenosis. Results of RT-PCR showed that the mutation (NM_001278939.1: c.1939G>T, p.Gly647Ter) did not affect the expression levels of ELN mRNA but increased protein level. The content of ELN truncate (functional component) was significantly lower in both the intracellular and extracellular compartments after mutation. These results indicate that the ELN mutation (NM_001278939.1: c.1939G>T, p.Gly647Ter) affected the protein truncate, which may be a functional component of ELN and play crucial roles for this pedigree. Here we report of an ELN heterozygous variant associated with congenital heart disease accompanied with pulmonary artery stenosis, which is less common. Based on our results, we speculate that this may be the main molecular mechanism underlying the mutation-led functional changes, and propose that the decrease of ELN protein level may cause this pedigree vascular abnormality, especially pulmonary artery stenosis, and reinforce the view that ELN insufficiency is the primary cause of these vascular lesions. This may be the main molecular mechanism underlying the mutation-led functional changes. Thus, systematic analysis not only enables us to better understand the etiology of this disease but also contributes to clinical and prenatal diagnosis.
format	article
author	Cuilan Hou Junmin Zheng Wei liu Lijian Xie Xiaomin Sun Yongwei Zhang Meng Xu Yun Li Tingting Xiao
author_facet	Cuilan Hou Junmin Zheng Wei liu Lijian Xie Xiaomin Sun Yongwei Zhang Meng Xu Yun Li Tingting Xiao
author_sort	Cuilan Hou
title	Identification and characterization of a novel ELN mutation in congenital heart disease with pulmonary artery stenosis
title_short	Identification and characterization of a novel ELN mutation in congenital heart disease with pulmonary artery stenosis
title_full	Identification and characterization of a novel ELN mutation in congenital heart disease with pulmonary artery stenosis
title_fullStr	Identification and characterization of a novel ELN mutation in congenital heart disease with pulmonary artery stenosis
title_full_unstemmed	Identification and characterization of a novel ELN mutation in congenital heart disease with pulmonary artery stenosis
title_sort	identification and characterization of a novel eln mutation in congenital heart disease with pulmonary artery stenosis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/466dd8c586fc48849f1138dc511088cb
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_version_	1718377855872663552

Identification and characterization of a novel ELN mutation in congenital heart disease with pulmonary artery stenosis

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