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Genetic testing and clinical relevance of patients with thoracic aortic aneurysm and dissection in northwestern China
BACKGROUND: Thoracic aortic aneurysm and dissection (TAAD) is a life‐threatening pathology that remains a challenge worldwide. Up to 40% of TAAD cases are hereditary with complex heterogeneous genetic backgrounds. The purposes of this study were to determine the diagnostic rate of patients with TAAD...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8580079/ https://www.ncbi.nlm.nih.gov/pubmed/34498425 http://dx.doi.org/10.1002/mgg3.1800 |
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author | Li, Jinjie Yang, Liu Diao, Yanjun Zhou, Lei Xin, Yijuan Jiang, Liqing Li, Rui Wang, Juan Duan, Weixun Liu, Jiayun |
author_facet | Li, Jinjie Yang, Liu Diao, Yanjun Zhou, Lei Xin, Yijuan Jiang, Liqing Li, Rui Wang, Juan Duan, Weixun Liu, Jiayun |
author_sort | Li, Jinjie |
collection | PubMed |
description | BACKGROUND: Thoracic aortic aneurysm and dissection (TAAD) is a life‐threatening pathology that remains a challenge worldwide. Up to 40% of TAAD cases are hereditary with complex heterogeneous genetic backgrounds. The purposes of this study were to determine the diagnostic rate of patients with TAAD, investigate the molecular pathologic spectrum of TAAD by next‐generation sequencing (NGS), and explore the future preclinical prospects of genetic diagnosis in patients at high ‐risk of study. METHODS: NGS was used to screen 15 genes associated with genetic TAAD in 212 patients from northwestern China. Clinical data of patients were gathered by electrocardiography, transthoracic echocardiography, and computed tomography. RESULTS: Of the 212 patients, 67 (31.60%) tested positive for a (likely) pathogenic variant, 42 (19.81%) had a variant of uncertain significance (VUS), and 103 (48.58%) had no variant (likely benign/benign/negative). A total of 135 reportable variants were detected in our test, among which 77 (57.04%) are first reported in this paper. A genotype–phenotype correlation of FBN1 was assessed, and the data showed that the patients with truncating and splicing mutations are more prone to developing severe aortic dissection than those with missense mutations, especially frameshift mutations (82.76% vs. 42.86%). In this study, 43 (20.28%) patients had a family history of sudden death or TAAD, whereas 132 (62.26%) did not (the remaining 37 were not available), and the positive rate of genetic testing was higher in TAAD patients with family history than in those without (76.74% vs. 18.94%). CONCLUSION: Our study concludes that genetic variation is an important consideration in the risk stratification of individualized prediction and disease diagnosis. |
format | Online Article Text |
id | pubmed-8580079 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85800792021-11-17 Genetic testing and clinical relevance of patients with thoracic aortic aneurysm and dissection in northwestern China Li, Jinjie Yang, Liu Diao, Yanjun Zhou, Lei Xin, Yijuan Jiang, Liqing Li, Rui Wang, Juan Duan, Weixun Liu, Jiayun Mol Genet Genomic Med Original Articles BACKGROUND: Thoracic aortic aneurysm and dissection (TAAD) is a life‐threatening pathology that remains a challenge worldwide. Up to 40% of TAAD cases are hereditary with complex heterogeneous genetic backgrounds. The purposes of this study were to determine the diagnostic rate of patients with TAAD, investigate the molecular pathologic spectrum of TAAD by next‐generation sequencing (NGS), and explore the future preclinical prospects of genetic diagnosis in patients at high ‐risk of study. METHODS: NGS was used to screen 15 genes associated with genetic TAAD in 212 patients from northwestern China. Clinical data of patients were gathered by electrocardiography, transthoracic echocardiography, and computed tomography. RESULTS: Of the 212 patients, 67 (31.60%) tested positive for a (likely) pathogenic variant, 42 (19.81%) had a variant of uncertain significance (VUS), and 103 (48.58%) had no variant (likely benign/benign/negative). A total of 135 reportable variants were detected in our test, among which 77 (57.04%) are first reported in this paper. A genotype–phenotype correlation of FBN1 was assessed, and the data showed that the patients with truncating and splicing mutations are more prone to developing severe aortic dissection than those with missense mutations, especially frameshift mutations (82.76% vs. 42.86%). In this study, 43 (20.28%) patients had a family history of sudden death or TAAD, whereas 132 (62.26%) did not (the remaining 37 were not available), and the positive rate of genetic testing was higher in TAAD patients with family history than in those without (76.74% vs. 18.94%). CONCLUSION: Our study concludes that genetic variation is an important consideration in the risk stratification of individualized prediction and disease diagnosis. John Wiley and Sons Inc. 2021-09-08 /pmc/articles/PMC8580079/ /pubmed/34498425 http://dx.doi.org/10.1002/mgg3.1800 Text en © 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Li, Jinjie Yang, Liu Diao, Yanjun Zhou, Lei Xin, Yijuan Jiang, Liqing Li, Rui Wang, Juan Duan, Weixun Liu, Jiayun Genetic testing and clinical relevance of patients with thoracic aortic aneurysm and dissection in northwestern China |
title | Genetic testing and clinical relevance of patients with thoracic aortic aneurysm and dissection in northwestern China |
title_full | Genetic testing and clinical relevance of patients with thoracic aortic aneurysm and dissection in northwestern China |
title_fullStr | Genetic testing and clinical relevance of patients with thoracic aortic aneurysm and dissection in northwestern China |
title_full_unstemmed | Genetic testing and clinical relevance of patients with thoracic aortic aneurysm and dissection in northwestern China |
title_short | Genetic testing and clinical relevance of patients with thoracic aortic aneurysm and dissection in northwestern China |
title_sort | genetic testing and clinical relevance of patients with thoracic aortic aneurysm and dissection in northwestern china |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8580079/ https://www.ncbi.nlm.nih.gov/pubmed/34498425 http://dx.doi.org/10.1002/mgg3.1800 |
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