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First genetic analysis of aneurysm genes in familial and sporadic abdominal aortic aneurysm
Genetic causes for abdominal aortic aneurysm (AAA) have not been identified and the role of genes associated with familial thoracic aneurysms in AAA has not been explored. We analyzed nine genes associated with familial thoracic aortic aneurysms, the vascular Ehlers–Danlos gene COL3A1 and the MTHFR...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4495250/ https://www.ncbi.nlm.nih.gov/pubmed/26017485 http://dx.doi.org/10.1007/s00439-015-1567-0 |
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author | van de Luijtgaarden, Koen M. Heijsman, Daphne Maugeri, Alessandra Weiss, Marjan M. Verhagen, Hence J. M. IJpma, Arne Brüggenwirth, Hennie T. Majoor-Krakauer, Danielle |
author_facet | van de Luijtgaarden, Koen M. Heijsman, Daphne Maugeri, Alessandra Weiss, Marjan M. Verhagen, Hence J. M. IJpma, Arne Brüggenwirth, Hennie T. Majoor-Krakauer, Danielle |
author_sort | van de Luijtgaarden, Koen M. |
collection | PubMed |
description | Genetic causes for abdominal aortic aneurysm (AAA) have not been identified and the role of genes associated with familial thoracic aneurysms in AAA has not been explored. We analyzed nine genes associated with familial thoracic aortic aneurysms, the vascular Ehlers–Danlos gene COL3A1 and the MTHFR p.Ala222Val variant in 155 AAA patients. The thoracic aneurysm genes selected for this study were the transforming growth factor-beta pathway genes EFEMP2, FBN1, SMAD3, TGBF2, TGFBR1, TGFBR2, and the smooth muscle cells genes ACTA2, MYH11 and MYLK. Sanger sequencing of all coding exons and exon–intron boundaries of these genes was performed. Patients with at least one first-degree relative with an aortic aneurysm were classified as familial AAA (n = 99), the others as sporadic AAA. We found 47 different rare heterozygous variants in eight genes: two pathogenic, one likely pathogenic, twenty-one variants of unknown significance (VUS) and twenty-three unlikely pathogenic variants. In familial AAA we found one pathogenic and segregating variant (COL3A1 p.Arg491X), one likely pathogenic and segregating (MYH11 p.Arg254Cys), and fifteen VUS. In sporadic patients we found one pathogenic (TGFBR2 p.Ile525Phefs*18) and seven VUS. Thirteen patients had two or more variants. These results show a previously unknown association and overlapping genetic defects between AAA and familial thoracic aneurysms, indicating that genetic testing may help to identify the cause of familial and sporadic AAA. In this view, genetic testing of these genes specifically or in a genome-wide approach may help to identify the cause of familial and sporadic AAA. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00439-015-1567-0) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4495250 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-44952502015-07-09 First genetic analysis of aneurysm genes in familial and sporadic abdominal aortic aneurysm van de Luijtgaarden, Koen M. Heijsman, Daphne Maugeri, Alessandra Weiss, Marjan M. Verhagen, Hence J. M. IJpma, Arne Brüggenwirth, Hennie T. Majoor-Krakauer, Danielle Hum Genet Original Investigation Genetic causes for abdominal aortic aneurysm (AAA) have not been identified and the role of genes associated with familial thoracic aneurysms in AAA has not been explored. We analyzed nine genes associated with familial thoracic aortic aneurysms, the vascular Ehlers–Danlos gene COL3A1 and the MTHFR p.Ala222Val variant in 155 AAA patients. The thoracic aneurysm genes selected for this study were the transforming growth factor-beta pathway genes EFEMP2, FBN1, SMAD3, TGBF2, TGFBR1, TGFBR2, and the smooth muscle cells genes ACTA2, MYH11 and MYLK. Sanger sequencing of all coding exons and exon–intron boundaries of these genes was performed. Patients with at least one first-degree relative with an aortic aneurysm were classified as familial AAA (n = 99), the others as sporadic AAA. We found 47 different rare heterozygous variants in eight genes: two pathogenic, one likely pathogenic, twenty-one variants of unknown significance (VUS) and twenty-three unlikely pathogenic variants. In familial AAA we found one pathogenic and segregating variant (COL3A1 p.Arg491X), one likely pathogenic and segregating (MYH11 p.Arg254Cys), and fifteen VUS. In sporadic patients we found one pathogenic (TGFBR2 p.Ile525Phefs*18) and seven VUS. Thirteen patients had two or more variants. These results show a previously unknown association and overlapping genetic defects between AAA and familial thoracic aneurysms, indicating that genetic testing may help to identify the cause of familial and sporadic AAA. In this view, genetic testing of these genes specifically or in a genome-wide approach may help to identify the cause of familial and sporadic AAA. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00439-015-1567-0) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2015-05-28 2015 /pmc/articles/PMC4495250/ /pubmed/26017485 http://dx.doi.org/10.1007/s00439-015-1567-0 Text en © The Author(s) 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Original Investigation van de Luijtgaarden, Koen M. Heijsman, Daphne Maugeri, Alessandra Weiss, Marjan M. Verhagen, Hence J. M. IJpma, Arne Brüggenwirth, Hennie T. Majoor-Krakauer, Danielle First genetic analysis of aneurysm genes in familial and sporadic abdominal aortic aneurysm |
title | First genetic analysis of aneurysm genes in familial and sporadic abdominal aortic aneurysm |
title_full | First genetic analysis of aneurysm genes in familial and sporadic abdominal aortic aneurysm |
title_fullStr | First genetic analysis of aneurysm genes in familial and sporadic abdominal aortic aneurysm |
title_full_unstemmed | First genetic analysis of aneurysm genes in familial and sporadic abdominal aortic aneurysm |
title_short | First genetic analysis of aneurysm genes in familial and sporadic abdominal aortic aneurysm |
title_sort | first genetic analysis of aneurysm genes in familial and sporadic abdominal aortic aneurysm |
topic | Original Investigation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4495250/ https://www.ncbi.nlm.nih.gov/pubmed/26017485 http://dx.doi.org/10.1007/s00439-015-1567-0 |
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