A Nonsense Variant Infbn1caused 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 parts per thousand. The causative variant ofFNB1gene accounts for approximately 70-80% of all MFS cases. In this study, we found a heterozygous c.3217G > T (p.Glu1073*) nonsense variant in theFBN1gene. This finding extended the variant spectrum of theFBN1gene 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 theFBN1gene, 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 ofFBN1cDNA in the patient was only about 21% compared to that of normal individuals. This variant c.3217G > T of theFBN1gene 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 theFBN1gene, which eventually led to Marfan syndrome in a Chinese family.