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Genetic screening for monogenic hypertension in hypertensive individuals in a clinical setting
BACKGROUND: Monogenic hypertension describe a series of hypertensive syndromes that are inherited by Mendelian laws. Sometimes genetic testing is required to provide evidence for their diagnoses, precise classification and targeted treatment. This study is the first to investigate the clinical utili...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418625/ https://www.ncbi.nlm.nih.gov/pubmed/32561571 http://dx.doi.org/10.1136/jmedgenet-2019-106145 |
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author | Bao, Minghui Li, Ping Li, Qifu Chen, Hui Zhong, Ying Li, Shuangyue Jin, Ling Wang, Wenjie Chen, Zhenzhen Zhong, Jiuchang Geng, Bin Fan, Yuxin Yang, Xinchun Cai, Jun |
author_facet | Bao, Minghui Li, Ping Li, Qifu Chen, Hui Zhong, Ying Li, Shuangyue Jin, Ling Wang, Wenjie Chen, Zhenzhen Zhong, Jiuchang Geng, Bin Fan, Yuxin Yang, Xinchun Cai, Jun |
author_sort | Bao, Minghui |
collection | PubMed |
description | BACKGROUND: Monogenic hypertension describe a series of hypertensive syndromes that are inherited by Mendelian laws. Sometimes genetic testing is required to provide evidence for their diagnoses, precise classification and targeted treatment. This study is the first to investigate the clinical utility of a causative gene screening and the combined yield of gene product expression analyses in cases with suspected monogenic hypertension. METHODS: We performed a large-scale multi-centre clinical genetic research of 1179 expertly selected hypertensive individuals from the Chinese Han population. Targeted sequencing were performed to evaluate 37 causative genes of potential cases of monogenic hypertension. Pathogenic and likely pathogenic variants were classified using the American College of Medical Genetics guidelines. Additionally, 49 variants of unknown significance (VUS) that had relatively high pathogenicity were selected and analysed using immunoblot protein expression assays. RESULTS: 21 pathogenic or likely pathogenic variants were identified in 33 of 1179 cases (2.80%). Gene product expression analyses showed 27 VUSs harboured by 49 individuals (4.16%) could lead to abnormally expressed protein levels. Consequently, combining genetic screening with gene product expression analyses increased the diagnostic yield from 2.80% to 6.79%. The main aetiologies established were primary aldosteronism (PA; 27, 2.29%) and pheochromocytoma and paraganglioma (PPGL; 10, 0.85%). CONCLUSION: Molecular diagnoses obtained using causative gene screening combined with gene product expression analyses initially achieved a modest diagnostic yield. Our data highlight the predominant roles of PA and PPGL. Furthermore, we provide evidence indicating the enhanced diagnostic ability of combined genetic and functional evaluation. |
format | Online Article Text |
id | pubmed-7418625 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-74186252020-08-18 Genetic screening for monogenic hypertension in hypertensive individuals in a clinical setting Bao, Minghui Li, Ping Li, Qifu Chen, Hui Zhong, Ying Li, Shuangyue Jin, Ling Wang, Wenjie Chen, Zhenzhen Zhong, Jiuchang Geng, Bin Fan, Yuxin Yang, Xinchun Cai, Jun J Med Genet Screening BACKGROUND: Monogenic hypertension describe a series of hypertensive syndromes that are inherited by Mendelian laws. Sometimes genetic testing is required to provide evidence for their diagnoses, precise classification and targeted treatment. This study is the first to investigate the clinical utility of a causative gene screening and the combined yield of gene product expression analyses in cases with suspected monogenic hypertension. METHODS: We performed a large-scale multi-centre clinical genetic research of 1179 expertly selected hypertensive individuals from the Chinese Han population. Targeted sequencing were performed to evaluate 37 causative genes of potential cases of monogenic hypertension. Pathogenic and likely pathogenic variants were classified using the American College of Medical Genetics guidelines. Additionally, 49 variants of unknown significance (VUS) that had relatively high pathogenicity were selected and analysed using immunoblot protein expression assays. RESULTS: 21 pathogenic or likely pathogenic variants were identified in 33 of 1179 cases (2.80%). Gene product expression analyses showed 27 VUSs harboured by 49 individuals (4.16%) could lead to abnormally expressed protein levels. Consequently, combining genetic screening with gene product expression analyses increased the diagnostic yield from 2.80% to 6.79%. The main aetiologies established were primary aldosteronism (PA; 27, 2.29%) and pheochromocytoma and paraganglioma (PPGL; 10, 0.85%). CONCLUSION: Molecular diagnoses obtained using causative gene screening combined with gene product expression analyses initially achieved a modest diagnostic yield. Our data highlight the predominant roles of PA and PPGL. Furthermore, we provide evidence indicating the enhanced diagnostic ability of combined genetic and functional evaluation. BMJ Publishing Group 2020-08 2020-06-19 /pmc/articles/PMC7418625/ /pubmed/32561571 http://dx.doi.org/10.1136/jmedgenet-2019-106145 Text en © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Screening Bao, Minghui Li, Ping Li, Qifu Chen, Hui Zhong, Ying Li, Shuangyue Jin, Ling Wang, Wenjie Chen, Zhenzhen Zhong, Jiuchang Geng, Bin Fan, Yuxin Yang, Xinchun Cai, Jun Genetic screening for monogenic hypertension in hypertensive individuals in a clinical setting |
title | Genetic screening for monogenic hypertension in hypertensive individuals in a clinical setting |
title_full | Genetic screening for monogenic hypertension in hypertensive individuals in a clinical setting |
title_fullStr | Genetic screening for monogenic hypertension in hypertensive individuals in a clinical setting |
title_full_unstemmed | Genetic screening for monogenic hypertension in hypertensive individuals in a clinical setting |
title_short | Genetic screening for monogenic hypertension in hypertensive individuals in a clinical setting |
title_sort | genetic screening for monogenic hypertension in hypertensive individuals in a clinical setting |
topic | Screening |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418625/ https://www.ncbi.nlm.nih.gov/pubmed/32561571 http://dx.doi.org/10.1136/jmedgenet-2019-106145 |
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