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Mutation screening in the FBN1 gene responsible for Marfan syndrome and related disorder in Chinese families
BACKGROUND: Previous studies showed that the fibrillin‐1 gene (FBN1) is responsible for Marfan sydrome (MFS) pathogenesis. This study is conducted to screen for mutations in the FBN1 gene in Chinese families with MFS. METHODS: Eight families with MFS and related disorder were recruited in this study...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6465674/ https://www.ncbi.nlm.nih.gov/pubmed/30838813 http://dx.doi.org/10.1002/mgg3.594 |
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author | Gong, Bo Yang, Lan Wang, Qingwei Ye, Zimeng Guo, Xiaoxin Yang, Chen Hao, Fang Shi, Yi Huang, Yi Qu, Chao Yang, Zhenglin |
author_facet | Gong, Bo Yang, Lan Wang, Qingwei Ye, Zimeng Guo, Xiaoxin Yang, Chen Hao, Fang Shi, Yi Huang, Yi Qu, Chao Yang, Zhenglin |
author_sort | Gong, Bo |
collection | PubMed |
description | BACKGROUND: Previous studies showed that the fibrillin‐1 gene (FBN1) is responsible for Marfan sydrome (MFS) pathogenesis. This study is conducted to screen for mutations in the FBN1 gene in Chinese families with MFS. METHODS: Eight families with MFS and related disorder were recruited in this study. All available family members underwent complete physical, ophthalmic, and cardiovascular examination. Mutation screening was performed using targeted next‐generation sequencing. Candidate variants were amplified by polymerase chain reaction and verified by direct Sanger sequencing. RESULTS: Four novel heterozygous mutations in FBN1, including c.2861G>T (p.R954L), c.4087G>A (p.D1363N), c.4987T>G (p.C1663G), and c.5032T>G (p.Y1678D), as well as four known mutations, c.3617G>A (p.G1206D), c.4460A>G (p.D1487G), c.4588C>T (p.R1530C), and c.718C>T (p.R240C) were identified. Affected patients from each family were found to carry one of the mutations, whereas the unaffected members and 1,086 normal controls were not. Each mutation was found to be cosegregated with MFS phenotype and related disorder in each family. Multiple sequence alignment of the human fibrillin‐1 protein showed that these mutations occurred in a highly conserved region among different species. CONCLUSIONS: Eight FBN1 mutations were identified in Chinese families with MFS and related disorder. These data expands FBN1 mutation spectrum and further emphasizes the role of FBN1 in the pathogenesis of MFS. |
format | Online Article Text |
id | pubmed-6465674 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-64656742019-04-23 Mutation screening in the FBN1 gene responsible for Marfan syndrome and related disorder in Chinese families Gong, Bo Yang, Lan Wang, Qingwei Ye, Zimeng Guo, Xiaoxin Yang, Chen Hao, Fang Shi, Yi Huang, Yi Qu, Chao Yang, Zhenglin Mol Genet Genomic Med Original Articles BACKGROUND: Previous studies showed that the fibrillin‐1 gene (FBN1) is responsible for Marfan sydrome (MFS) pathogenesis. This study is conducted to screen for mutations in the FBN1 gene in Chinese families with MFS. METHODS: Eight families with MFS and related disorder were recruited in this study. All available family members underwent complete physical, ophthalmic, and cardiovascular examination. Mutation screening was performed using targeted next‐generation sequencing. Candidate variants were amplified by polymerase chain reaction and verified by direct Sanger sequencing. RESULTS: Four novel heterozygous mutations in FBN1, including c.2861G>T (p.R954L), c.4087G>A (p.D1363N), c.4987T>G (p.C1663G), and c.5032T>G (p.Y1678D), as well as four known mutations, c.3617G>A (p.G1206D), c.4460A>G (p.D1487G), c.4588C>T (p.R1530C), and c.718C>T (p.R240C) were identified. Affected patients from each family were found to carry one of the mutations, whereas the unaffected members and 1,086 normal controls were not. Each mutation was found to be cosegregated with MFS phenotype and related disorder in each family. Multiple sequence alignment of the human fibrillin‐1 protein showed that these mutations occurred in a highly conserved region among different species. CONCLUSIONS: Eight FBN1 mutations were identified in Chinese families with MFS and related disorder. These data expands FBN1 mutation spectrum and further emphasizes the role of FBN1 in the pathogenesis of MFS. John Wiley and Sons Inc. 2019-03-05 /pmc/articles/PMC6465674/ /pubmed/30838813 http://dx.doi.org/10.1002/mgg3.594 Text en © 2019 School of Medicine, University of Electronic Science and Technology of China. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Gong, Bo Yang, Lan Wang, Qingwei Ye, Zimeng Guo, Xiaoxin Yang, Chen Hao, Fang Shi, Yi Huang, Yi Qu, Chao Yang, Zhenglin Mutation screening in the FBN1 gene responsible for Marfan syndrome and related disorder in Chinese families |
title | Mutation screening in the FBN1 gene responsible for Marfan syndrome and related disorder in Chinese families |
title_full | Mutation screening in the FBN1 gene responsible for Marfan syndrome and related disorder in Chinese families |
title_fullStr | Mutation screening in the FBN1 gene responsible for Marfan syndrome and related disorder in Chinese families |
title_full_unstemmed | Mutation screening in the FBN1 gene responsible for Marfan syndrome and related disorder in Chinese families |
title_short | Mutation screening in the FBN1 gene responsible for Marfan syndrome and related disorder in Chinese families |
title_sort | mutation screening in the fbn1 gene responsible for marfan syndrome and related disorder in chinese families |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6465674/ https://www.ncbi.nlm.nih.gov/pubmed/30838813 http://dx.doi.org/10.1002/mgg3.594 |
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