Dataset Information

A novel mutation in FBN1 gene in autosomal dominant Marfan syndrome and macular degeneration in a Chinese consanguineous family.

ABSTRACT:

Aim

To report a novel mutation in FBN1 gene in a Chinese consanguineous family with common Marfan syndrome (MFS) phenotype and an unusual bilateral macular degeneration.

Methods

Ophthalmic, cardiovascular and systemic examinations were performed, and genomic DNA extracted from all living family members. The 24-32 exon mutations of FBN1 gene were screened by Sanger Sequencing in all family members and 100 unrelated healthy Chinese individuals.

Results

In the four-generation family, classic MFS phenotypes were observed in all 5 patients, 2 of them had peculiar phenotype of bilateral macular degeneration. Mutation screening in FBN1 identified a heterozygous missense mutation (c.3932A>G, p.Y1311C) with co-segregation. This mutation was found with the MFS phenotypes in all 5 patients but not in unaffected members or unrelated controls.

Conclusion

A Chinese consanguineous MFS family with uncommon bilateral macular degeneration and an unreported c.3932A>G mutation in FBN1 was identified. Our finding expands the FBN1 mutation spectrum and its possible role in the pathogenesis of Marfan syndrome.

SUBMITTER: Ouyang PB

PROVIDER: S-EPMC6520272 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

A novel mutation in <i>FBN1</i> gene in autosomal dominant Marfan syndrome and macular degeneration in a Chinese consanguineous family.

Ouyang Ping-Bo PB Zhao Yuan Y Peng Ying-Qian YQ Zhang Lu-Si LS Cao Jian J Li Yun Y

International journal of ophthalmology 20190518 5

<h4>Aim</h4>To report a novel mutation in <i>FBN1</i> gene in a Chinese consanguineous family with common Marfan syndrome (MFS) phenotype and an unusual bilateral macular degeneration.<h4>Methods</h4>Ophthalmic, cardiovascular and systemic examinations were performed, and genomic DNA extracted from all living family members. The 24-32 exon mutations of <i>FBN1</i> gene were screened by Sanger Sequencing in all family members and 100 unrelated healthy Chinese individuals.<h4>Results</h4>In the fo ...[more]

PMID: 31131229

Similar Datasets

Project description:BackgroundMarfan 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 presentationThe 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.ConclusionsIn 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.