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Identification of gross deletions in FBN1 gene by MLPA

BACKGROUND: Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder caused by mutations in the FBN1 gene. Approximately 90% of classic MFS patients have a FBN1 mutation that can be identified by single-gene sequencing or gene-panel sequencing targeting FBN1. However, a small propor...

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Autores principales: Yang, Hang, Ma, Yanyun, Luo, Mingyao, Zhao, Kun, Zhang, Yinhui, Zhu, Guoyan, Sun, Xiaogang, Luo, Fanyan, Wang, Lin, Shu, Chang, Zhou, Zhou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172713/
https://www.ncbi.nlm.nih.gov/pubmed/30286810
http://dx.doi.org/10.1186/s40246-018-0178-y
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author Yang, Hang
Ma, Yanyun
Luo, Mingyao
Zhao, Kun
Zhang, Yinhui
Zhu, Guoyan
Sun, Xiaogang
Luo, Fanyan
Wang, Lin
Shu, Chang
Zhou, Zhou
author_facet Yang, Hang
Ma, Yanyun
Luo, Mingyao
Zhao, Kun
Zhang, Yinhui
Zhu, Guoyan
Sun, Xiaogang
Luo, Fanyan
Wang, Lin
Shu, Chang
Zhou, Zhou
author_sort Yang, Hang
collection PubMed
description BACKGROUND: Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder caused by mutations in the FBN1 gene. Approximately 90% of classic MFS patients have a FBN1 mutation that can be identified by single-gene sequencing or gene-panel sequencing targeting FBN1. However, a small proportion of MFS patients carry a large genomic deletion in FBN1, which cannot be detected by routine sequencing. Here, we performed an MLPA (multiplex ligation-dependent probe amplification) test to detect large deletions and/or duplications in FBN1 and TGFBR2 in 115 unrelated Chinese patients with suspected MFS or early-onset aneurysm/dissection. RESULTS: Five novel large deletions encompassing a single exon or multiple exons in the FBN1 gene were characterized in five unrelated patients, of which four were proven by Sanger sequencing, and the breakpoints were identified. Three of them met the revised Ghent criteria when genetic results were not available, and the other two patients were highly suspected and diagnosed with MFS until the FBN1 deletions were identified. CONCLUSIONS: Our finding expands the mutation spectrum of large FBN1 deletions and emphasizes the importance of screening for large FBN1 deletions in clinical genetic testing, especially for those with classic Marfan phenotype. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40246-018-0178-y) contains supplementary material, which is available to authorized users.
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spelling pubmed-61727132018-10-10 Identification of gross deletions in FBN1 gene by MLPA Yang, Hang Ma, Yanyun Luo, Mingyao Zhao, Kun Zhang, Yinhui Zhu, Guoyan Sun, Xiaogang Luo, Fanyan Wang, Lin Shu, Chang Zhou, Zhou Hum Genomics Primary Research BACKGROUND: Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder caused by mutations in the FBN1 gene. Approximately 90% of classic MFS patients have a FBN1 mutation that can be identified by single-gene sequencing or gene-panel sequencing targeting FBN1. However, a small proportion of MFS patients carry a large genomic deletion in FBN1, which cannot be detected by routine sequencing. Here, we performed an MLPA (multiplex ligation-dependent probe amplification) test to detect large deletions and/or duplications in FBN1 and TGFBR2 in 115 unrelated Chinese patients with suspected MFS or early-onset aneurysm/dissection. RESULTS: Five novel large deletions encompassing a single exon or multiple exons in the FBN1 gene were characterized in five unrelated patients, of which four were proven by Sanger sequencing, and the breakpoints were identified. Three of them met the revised Ghent criteria when genetic results were not available, and the other two patients were highly suspected and diagnosed with MFS until the FBN1 deletions were identified. CONCLUSIONS: Our finding expands the mutation spectrum of large FBN1 deletions and emphasizes the importance of screening for large FBN1 deletions in clinical genetic testing, especially for those with classic Marfan phenotype. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40246-018-0178-y) contains supplementary material, which is available to authorized users. BioMed Central 2018-10-04 /pmc/articles/PMC6172713/ /pubmed/30286810 http://dx.doi.org/10.1186/s40246-018-0178-y Text en © The Author(s). 2018 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. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Primary Research
Yang, Hang
Ma, Yanyun
Luo, Mingyao
Zhao, Kun
Zhang, Yinhui
Zhu, Guoyan
Sun, Xiaogang
Luo, Fanyan
Wang, Lin
Shu, Chang
Zhou, Zhou
Identification of gross deletions in FBN1 gene by MLPA
title Identification of gross deletions in FBN1 gene by MLPA
title_full Identification of gross deletions in FBN1 gene by MLPA
title_fullStr Identification of gross deletions in FBN1 gene by MLPA
title_full_unstemmed Identification of gross deletions in FBN1 gene by MLPA
title_short Identification of gross deletions in FBN1 gene by MLPA
title_sort identification of gross deletions in fbn1 gene by mlpa
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172713/
https://www.ncbi.nlm.nih.gov/pubmed/30286810
http://dx.doi.org/10.1186/s40246-018-0178-y
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