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A nonsense variant in FBN1 caused autosomal dominant Marfan syndrome in a Chinese family: a case report
BACKGROUND: Marfan syndrome (MFS) is a common autosomal dominant inherited disease, and the occurrence rate is around 0.1–0.2‰. The causative variant of FNB1 gene accounts for approximately 70–80% of all MFS cases. In this study, we found a heterozygous c.3217G > T (p.Glu1073*) nonsense variant i...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579915/ https://www.ncbi.nlm.nih.gov/pubmed/33087052 http://dx.doi.org/10.1186/s12881-020-01148-1 |
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author | Niu, Yuping Huang, Sexin Wang, Zeyu Xu, Peiwen Wang, Lijuan Li, Jie Gao, Ming Gao, Xuan Gao, Yuan |
author_facet | Niu, Yuping Huang, Sexin Wang, Zeyu Xu, Peiwen Wang, Lijuan Li, Jie Gao, Ming Gao, Xuan Gao, Yuan |
author_sort | Niu, Yuping |
collection | PubMed |
description | BACKGROUND: Marfan syndrome (MFS) is a common autosomal dominant inherited disease, and the occurrence rate is around 0.1–0.2‰. The causative variant of FNB1 gene accounts for approximately 70–80% of all MFS cases. In this study, we found a heterozygous c.3217G > T (p.Glu1073*) nonsense variant in the FBN1 gene. This finding extended the variant spectrum of the FBN1 gene and will provide a solution for patients to bear healthy offspring by preimplantation genetic testing or prenatal diagnosis. CASE PRESENTATION: The patient was treated due to tachycardia during excitement in a hospital. Echocardiography showed dilatation of the ascending aorta and main pulmonary artery, mitral regurgitation (mild), tricuspid regurgitation (mild), and abnormal left ventricular filling. Electrocardiograph showed sinus rhythm. In addition, flutters of shadows in front of his eyes and vitreous opacity were present in the patient. Genomic DNA was extracted from peripheral blood samples from members of the family and 100 unrelated controls. Potential variants were screened out by next-generation sequencing and confirmed by MLPA & Sanger sequencing. Real-time fluorescence quantitative PCR (RT-qPCR) was performed to detect the relative mRNA quantitation in the patient. A heterozygous nonsense variant c.3217G > T of the FBN1 gene, which resulted in p. Glu1073Term, was identified in both patients. Only wild type bases were found in the cDNA sequence of the patient. Real-time fluorogenic quantitative PCR results showed that the relative expression level of FBN1 cDNA in the patient was only about 21% compared to that of normal individuals. This variant c.3217G > T of the FBN1 gene introduces a Stop codon in the cb-EGF12 domain. We speculated that a premature translational-termination codon (PTC) was located in the mRNA and the target mRNA was disintegrated through a process known as nonsense-mediated mRNA decay (NMD), which led to a significant decrease of the fibrillin-1 protein, eventually causing clinical symptoms in the patient. CONCLUSIONS: In this study, we found a heterozygous c.3217G > T (p.Glu1073*) nonsense variant in the FBN1 gene, which eventually led to Marfan syndrome in a Chinese family. |
format | Online Article Text |
id | pubmed-7579915 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-75799152020-10-22 A nonsense variant in FBN1 caused autosomal dominant Marfan syndrome in a Chinese family: a case report Niu, Yuping Huang, Sexin Wang, Zeyu Xu, Peiwen Wang, Lijuan Li, Jie Gao, Ming Gao, Xuan Gao, Yuan BMC Med Genet Case Report BACKGROUND: Marfan syndrome (MFS) is a common autosomal dominant inherited disease, and the occurrence rate is around 0.1–0.2‰. The causative variant of FNB1 gene accounts for approximately 70–80% of all MFS cases. In this study, we found a heterozygous c.3217G > T (p.Glu1073*) nonsense variant in the FBN1 gene. This finding extended the variant spectrum of the FBN1 gene and will provide a solution for patients to bear healthy offspring by preimplantation genetic testing or prenatal diagnosis. CASE PRESENTATION: The patient was treated due to tachycardia during excitement in a hospital. Echocardiography showed dilatation of the ascending aorta and main pulmonary artery, mitral regurgitation (mild), tricuspid regurgitation (mild), and abnormal left ventricular filling. Electrocardiograph showed sinus rhythm. In addition, flutters of shadows in front of his eyes and vitreous opacity were present in the patient. Genomic DNA was extracted from peripheral blood samples from members of the family and 100 unrelated controls. Potential variants were screened out by next-generation sequencing and confirmed by MLPA & Sanger sequencing. Real-time fluorescence quantitative PCR (RT-qPCR) was performed to detect the relative mRNA quantitation in the patient. A heterozygous nonsense variant c.3217G > T of the FBN1 gene, which resulted in p. Glu1073Term, was identified in both patients. Only wild type bases were found in the cDNA sequence of the patient. Real-time fluorogenic quantitative PCR results showed that the relative expression level of FBN1 cDNA in the patient was only about 21% compared to that of normal individuals. This variant c.3217G > T of the FBN1 gene introduces a Stop codon in the cb-EGF12 domain. We speculated that a premature translational-termination codon (PTC) was located in the mRNA and the target mRNA was disintegrated through a process known as nonsense-mediated mRNA decay (NMD), which led to a significant decrease of the fibrillin-1 protein, eventually causing clinical symptoms in the patient. CONCLUSIONS: In this study, we found a heterozygous c.3217G > T (p.Glu1073*) nonsense variant in the FBN1 gene, which eventually led to Marfan syndrome in a Chinese family. BioMed Central 2020-10-21 /pmc/articles/PMC7579915/ /pubmed/33087052 http://dx.doi.org/10.1186/s12881-020-01148-1 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data. |
spellingShingle | Case Report Niu, Yuping Huang, Sexin Wang, Zeyu Xu, Peiwen Wang, Lijuan Li, Jie Gao, Ming Gao, Xuan Gao, Yuan A nonsense variant in FBN1 caused autosomal dominant Marfan syndrome in a Chinese family: a case report |
title | A nonsense variant in FBN1 caused autosomal dominant Marfan syndrome in a Chinese family: a case report |
title_full | A nonsense variant in FBN1 caused autosomal dominant Marfan syndrome in a Chinese family: a case report |
title_fullStr | A nonsense variant in FBN1 caused autosomal dominant Marfan syndrome in a Chinese family: a case report |
title_full_unstemmed | A nonsense variant in FBN1 caused autosomal dominant Marfan syndrome in a Chinese family: a case report |
title_short | A nonsense variant in FBN1 caused autosomal dominant Marfan syndrome in a Chinese family: a case report |
title_sort | nonsense variant in fbn1 caused autosomal dominant marfan syndrome in a chinese family: a case report |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579915/ https://www.ncbi.nlm.nih.gov/pubmed/33087052 http://dx.doi.org/10.1186/s12881-020-01148-1 |
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