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Application of Whole Exome Sequencing and Functional Annotations to Identify Genetic Variants Associated with Marfan Syndrome

Marfan syndrome (MFS) is a rare disease that affects connective tissue, which causes abnormalities in several organ systems including the heart, eyes, bones, and joints. The autosomal dominant disorder was found to be strongly associated with FBN1, TGFBR1, and TGFBR2 mutations. Although multiple gen...

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Autores principales: Lin, Min-Rou, Chang, Che-Mai, Ting, Jafit, Chang, Jan-Gowth, Chou, Wan-Hsuan, Huang, Kuei-Jung, Cheng, Gloria, Chang, Hsiao-Huang, Chang, Wei-Chiao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8878617/
https://www.ncbi.nlm.nih.gov/pubmed/35207686
http://dx.doi.org/10.3390/jpm12020198
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author Lin, Min-Rou
Chang, Che-Mai
Ting, Jafit
Chang, Jan-Gowth
Chou, Wan-Hsuan
Huang, Kuei-Jung
Cheng, Gloria
Chang, Hsiao-Huang
Chang, Wei-Chiao
author_facet Lin, Min-Rou
Chang, Che-Mai
Ting, Jafit
Chang, Jan-Gowth
Chou, Wan-Hsuan
Huang, Kuei-Jung
Cheng, Gloria
Chang, Hsiao-Huang
Chang, Wei-Chiao
author_sort Lin, Min-Rou
collection PubMed
description Marfan syndrome (MFS) is a rare disease that affects connective tissue, which causes abnormalities in several organ systems including the heart, eyes, bones, and joints. The autosomal dominant disorder was found to be strongly associated with FBN1, TGFBR1, and TGFBR2 mutations. Although multiple genetic mutations have been reported, data from Asian populations are still limited. As a result, we utilized the whole exome sequencing (WES) technique to identify potential pathogenic variants of MFS in a Taiwan cohort. In addition, a variety of annotation databases were applied to identify the biological functions as well as the potential mechanisms of candidate genes. In this study, we confirmed the pathogenicity of FBN1 to MFS. Our results indicated that TTN and POMT1 may be likely related to MFS phenotypes. Furthermore, we found nine unique variants highly shared in a MFS family cohort, of which eight are novel variants worthy of further investigation.
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spelling pubmed-88786172022-02-26 Application of Whole Exome Sequencing and Functional Annotations to Identify Genetic Variants Associated with Marfan Syndrome Lin, Min-Rou Chang, Che-Mai Ting, Jafit Chang, Jan-Gowth Chou, Wan-Hsuan Huang, Kuei-Jung Cheng, Gloria Chang, Hsiao-Huang Chang, Wei-Chiao J Pers Med Article Marfan syndrome (MFS) is a rare disease that affects connective tissue, which causes abnormalities in several organ systems including the heart, eyes, bones, and joints. The autosomal dominant disorder was found to be strongly associated with FBN1, TGFBR1, and TGFBR2 mutations. Although multiple genetic mutations have been reported, data from Asian populations are still limited. As a result, we utilized the whole exome sequencing (WES) technique to identify potential pathogenic variants of MFS in a Taiwan cohort. In addition, a variety of annotation databases were applied to identify the biological functions as well as the potential mechanisms of candidate genes. In this study, we confirmed the pathogenicity of FBN1 to MFS. Our results indicated that TTN and POMT1 may be likely related to MFS phenotypes. Furthermore, we found nine unique variants highly shared in a MFS family cohort, of which eight are novel variants worthy of further investigation. MDPI 2022-02-01 /pmc/articles/PMC8878617/ /pubmed/35207686 http://dx.doi.org/10.3390/jpm12020198 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lin, Min-Rou
Chang, Che-Mai
Ting, Jafit
Chang, Jan-Gowth
Chou, Wan-Hsuan
Huang, Kuei-Jung
Cheng, Gloria
Chang, Hsiao-Huang
Chang, Wei-Chiao
Application of Whole Exome Sequencing and Functional Annotations to Identify Genetic Variants Associated with Marfan Syndrome
title Application of Whole Exome Sequencing and Functional Annotations to Identify Genetic Variants Associated with Marfan Syndrome
title_full Application of Whole Exome Sequencing and Functional Annotations to Identify Genetic Variants Associated with Marfan Syndrome
title_fullStr Application of Whole Exome Sequencing and Functional Annotations to Identify Genetic Variants Associated with Marfan Syndrome
title_full_unstemmed Application of Whole Exome Sequencing and Functional Annotations to Identify Genetic Variants Associated with Marfan Syndrome
title_short Application of Whole Exome Sequencing and Functional Annotations to Identify Genetic Variants Associated with Marfan Syndrome
title_sort application of whole exome sequencing and functional annotations to identify genetic variants associated with marfan syndrome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8878617/
https://www.ncbi.nlm.nih.gov/pubmed/35207686
http://dx.doi.org/10.3390/jpm12020198
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