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A Novel Splice-Site Mutation in the ELN Gene Suggests an Alternative Mechanism for Vascular Elastinopathies
The ELN gene encodes elastin, a fundamental protein of the extracellular matrix that confers elasticity to different tissues including blood vessels. The formation of elastin fibers is a complex process involving monomer coacervation and subsequent crosslinking. Mutations in exons 1–29 of the ELN ge...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751611/ https://www.ncbi.nlm.nih.gov/pubmed/33364810 http://dx.doi.org/10.2147/TACG.S282240 |
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author | Velandia-Piedrahita, Camilo Andres Morel, Adrien Fonseca-Mendoza, Dora Janeth Huertas-Quiñones, Victor Manuel Castillo, David Bonilla, Juan Diego Hernandez-Toro, Camilo José Miranda-Fernández, Marta Catalina Restrepo, Carlos Martin Cabrera, Rodrigo |
author_facet | Velandia-Piedrahita, Camilo Andres Morel, Adrien Fonseca-Mendoza, Dora Janeth Huertas-Quiñones, Victor Manuel Castillo, David Bonilla, Juan Diego Hernandez-Toro, Camilo José Miranda-Fernández, Marta Catalina Restrepo, Carlos Martin Cabrera, Rodrigo |
author_sort | Velandia-Piedrahita, Camilo Andres |
collection | PubMed |
description | The ELN gene encodes elastin, a fundamental protein of the extracellular matrix that confers elasticity to different tissues including blood vessels. The formation of elastin fibers is a complex process involving monomer coacervation and subsequent crosslinking. Mutations in exons 1–29 of the ELN gene have been linked to supravalvular aortic stenosis (SVAS) whereas mutations in exons 30–33 are associated with autosomal dominant cutis laxa (ADCL). This striking segregation has led to the hypothesis that distinct molecular mechanisms underlie both diseases. SVAS is believed to arise through haploinsufficiency while ADCL is hypothesized to be caused by a dominant negative effect. Here, we describe a patient with SVAS harboring a novel splice-site mutation in the last exon of ELN. The location of this mutation is not consistent with current knowledge of SVAS, since all mutations reported in the C-terminus have been found in ADCL patients, and a thorough evaluation did not reveal significant skin involvement in this case. RT-PCR analysis of skin tissue showed that C-terminal mutations in the region can lead to the production of aberrant transcripts through intron retention and activation of cryptic splice sites and suggest that disruption of the very last exon can lead to functional haploinsufficiency potentially related to SVAS. |
format | Online Article Text |
id | pubmed-7751611 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-77516112020-12-22 A Novel Splice-Site Mutation in the ELN Gene Suggests an Alternative Mechanism for Vascular Elastinopathies Velandia-Piedrahita, Camilo Andres Morel, Adrien Fonseca-Mendoza, Dora Janeth Huertas-Quiñones, Victor Manuel Castillo, David Bonilla, Juan Diego Hernandez-Toro, Camilo José Miranda-Fernández, Marta Catalina Restrepo, Carlos Martin Cabrera, Rodrigo Appl Clin Genet Case Report The ELN gene encodes elastin, a fundamental protein of the extracellular matrix that confers elasticity to different tissues including blood vessels. The formation of elastin fibers is a complex process involving monomer coacervation and subsequent crosslinking. Mutations in exons 1–29 of the ELN gene have been linked to supravalvular aortic stenosis (SVAS) whereas mutations in exons 30–33 are associated with autosomal dominant cutis laxa (ADCL). This striking segregation has led to the hypothesis that distinct molecular mechanisms underlie both diseases. SVAS is believed to arise through haploinsufficiency while ADCL is hypothesized to be caused by a dominant negative effect. Here, we describe a patient with SVAS harboring a novel splice-site mutation in the last exon of ELN. The location of this mutation is not consistent with current knowledge of SVAS, since all mutations reported in the C-terminus have been found in ADCL patients, and a thorough evaluation did not reveal significant skin involvement in this case. RT-PCR analysis of skin tissue showed that C-terminal mutations in the region can lead to the production of aberrant transcripts through intron retention and activation of cryptic splice sites and suggest that disruption of the very last exon can lead to functional haploinsufficiency potentially related to SVAS. Dove 2020-12-17 /pmc/articles/PMC7751611/ /pubmed/33364810 http://dx.doi.org/10.2147/TACG.S282240 Text en © 2020 Velandia-Piedrahita et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Case Report Velandia-Piedrahita, Camilo Andres Morel, Adrien Fonseca-Mendoza, Dora Janeth Huertas-Quiñones, Victor Manuel Castillo, David Bonilla, Juan Diego Hernandez-Toro, Camilo José Miranda-Fernández, Marta Catalina Restrepo, Carlos Martin Cabrera, Rodrigo A Novel Splice-Site Mutation in the ELN Gene Suggests an Alternative Mechanism for Vascular Elastinopathies |
title | A Novel Splice-Site Mutation in the ELN Gene Suggests an Alternative Mechanism for Vascular Elastinopathies |
title_full | A Novel Splice-Site Mutation in the ELN Gene Suggests an Alternative Mechanism for Vascular Elastinopathies |
title_fullStr | A Novel Splice-Site Mutation in the ELN Gene Suggests an Alternative Mechanism for Vascular Elastinopathies |
title_full_unstemmed | A Novel Splice-Site Mutation in the ELN Gene Suggests an Alternative Mechanism for Vascular Elastinopathies |
title_short | A Novel Splice-Site Mutation in the ELN Gene Suggests an Alternative Mechanism for Vascular Elastinopathies |
title_sort | novel splice-site mutation in the eln gene suggests an alternative mechanism for vascular elastinopathies |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751611/ https://www.ncbi.nlm.nih.gov/pubmed/33364810 http://dx.doi.org/10.2147/TACG.S282240 |
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