A nonsense variant in FBN1 caused autosomal dominant Marfan syndrome in a Chinese family: a case report
Abstract 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 v...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2020-10-01
|
| Series: | BMC Medical Genetics |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12881-020-01148-1 |
| _version_ | 1818721254891323392 |
|---|---|
| author | Yuping Niu Sexin Huang Zeyu Wang Peiwen Xu Lijuan Wang Jie Li Ming Gao Xuan Gao Yuan Gao |
| author_facet | Yuping Niu Sexin Huang Zeyu Wang Peiwen Xu Lijuan Wang Jie Li Ming Gao Xuan Gao Yuan Gao |
| author_sort | Yuping Niu |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-17T20:35:49Z |
| format | Article |
| id | doaj.art-746fc289db1c42b880a4099c49aa7a7e |
| institution | Directory Open Access Journal |
| issn | 1471-2350 |
| language | English |
| last_indexed | 2024-12-17T20:35:49Z |
| publishDate | 2020-10-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genetics |
| spelling | doaj.art-746fc289db1c42b880a4099c49aa7a7e2022-12-21T21:33:26ZengBMCBMC Medical Genetics1471-23502020-10-012111710.1186/s12881-020-01148-1A nonsense variant in FBN1 caused autosomal dominant Marfan syndrome in a Chinese family: a case reportYuping Niu0Sexin Huang1Zeyu Wang2Peiwen Xu3Lijuan Wang4Jie Li5Ming Gao6Xuan Gao7Yuan Gao8Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong UniversityCenter for Reproductive Medicine, Cheeloo College of Medicine, Shandong UniversityGeorgia Institute of TechnologyCenter for Reproductive Medicine, Cheeloo College of Medicine, Shandong UniversityCenter for Reproductive Medicine, Cheeloo College of Medicine, Shandong UniversityCenter for Reproductive Medicine, Cheeloo College of Medicine, Shandong UniversityCenter for Reproductive Medicine, Cheeloo College of Medicine, Shandong UniversityCenter for Reproductive Medicine, Cheeloo College of Medicine, Shandong UniversityCenter for Reproductive Medicine, Cheeloo College of Medicine, Shandong UniversityAbstract 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.http://link.springer.com/article/10.1186/s12881-020-01148-1Marfan syndromeFBN1 geneNonsense variantNonsense-mediated mRNA decay |
| spellingShingle | Yuping Niu Sexin Huang Zeyu Wang Peiwen Xu Lijuan Wang Jie Li Ming Gao Xuan Gao Yuan Gao A nonsense variant in FBN1 caused autosomal dominant Marfan syndrome in a Chinese family: a case report BMC Medical Genetics Marfan syndrome FBN1 gene Nonsense variant Nonsense-mediated mRNA decay |
| 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 | Marfan syndrome FBN1 gene Nonsense variant Nonsense-mediated mRNA decay |
| url | http://link.springer.com/article/10.1186/s12881-020-01148-1 |
| work_keys_str_mv | AT yupingniu anonsensevariantinfbn1causedautosomaldominantmarfansyndromeinachinesefamilyacasereport AT sexinhuang anonsensevariantinfbn1causedautosomaldominantmarfansyndromeinachinesefamilyacasereport AT zeyuwang anonsensevariantinfbn1causedautosomaldominantmarfansyndromeinachinesefamilyacasereport AT peiwenxu anonsensevariantinfbn1causedautosomaldominantmarfansyndromeinachinesefamilyacasereport AT lijuanwang anonsensevariantinfbn1causedautosomaldominantmarfansyndromeinachinesefamilyacasereport AT jieli anonsensevariantinfbn1causedautosomaldominantmarfansyndromeinachinesefamilyacasereport AT minggao anonsensevariantinfbn1causedautosomaldominantmarfansyndromeinachinesefamilyacasereport AT xuangao anonsensevariantinfbn1causedautosomaldominantmarfansyndromeinachinesefamilyacasereport AT yuangao anonsensevariantinfbn1causedautosomaldominantmarfansyndromeinachinesefamilyacasereport AT yupingniu nonsensevariantinfbn1causedautosomaldominantmarfansyndromeinachinesefamilyacasereport AT sexinhuang nonsensevariantinfbn1causedautosomaldominantmarfansyndromeinachinesefamilyacasereport AT zeyuwang nonsensevariantinfbn1causedautosomaldominantmarfansyndromeinachinesefamilyacasereport AT peiwenxu nonsensevariantinfbn1causedautosomaldominantmarfansyndromeinachinesefamilyacasereport AT lijuanwang nonsensevariantinfbn1causedautosomaldominantmarfansyndromeinachinesefamilyacasereport AT jieli nonsensevariantinfbn1causedautosomaldominantmarfansyndromeinachinesefamilyacasereport AT minggao nonsensevariantinfbn1causedautosomaldominantmarfansyndromeinachinesefamilyacasereport AT xuangao nonsensevariantinfbn1causedautosomaldominantmarfansyndromeinachinesefamilyacasereport AT yuangao nonsensevariantinfbn1causedautosomaldominantmarfansyndromeinachinesefamilyacasereport |