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Novel FBN1 mutations are responsible for cardiovascular manifestations of Marfan syndrome

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Abstract

The fibrillin-1 (FBN1) gene mutations result in Marfan syndrome (MFS) and have a variety of phenotypic variations. This disease is involved in the skeletal, ocular and cardiovascular system. Here we analyzed genotype-phenotype correlation in two Chinese families with MFS. Two patients with thoracic aortic aneurysms and dissections were diagnosed as MFS according to the revised Ghent criteria. Peripheral blood samples were collected and genomic DNAs were isolated from available cases, namely, patient-1 and his daughter and son, and patient-2 and his parents. According to the next-generation sequencing results, the mutations in FBN1 were confirmed by direct sequencing. A heterozygous frameshift mutation in exon 12 of FBN1 was found in the proband-1 and his daughter. They showed cardiovascular phenotype thoracic aortic aneurysms and dissections, a life-threatening vascular disease, and atrial septal defect respectively. One de novo missense mutation in exon 50 of FBN1 was identified only in the patient-2, showing aortic root aneurysm and aortic root dilatation. Intriguingly, two novel mutations mainly caused the cardiovascular complications in affected family members. No meaningful mutations were found in these two patients by screening all exons of 428 genes related with cardiovascular disease. The high incidence of cardiovascular manifestations might be associated with the two novel mutations in exon 12 and 50 of FBN1.

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Acknowledgments

The study was supported by National Natural Science Foundation of China with Grants 81322002 and 81270333 to Dr. Wang.

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Authors and Affiliations

  1. College of Medical Science, China Three Gorges University, Yichang, Hubei, China

    Jin’e Wang

  2. State Key Laboratory of Cardiovascular Disease, Sino-German Laboratory for Molecular Medicine, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Rd, Beijing, 100037, China

    Jin’e Wang, Yupeng Yan, Jinxing Chen, Ling Gong, Yu Zhang, Mengmeng Yuan, Bing Cui & Yibo Wang

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  1. Jin’e Wang
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  2. Yupeng Yan
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  3. Jinxing Chen
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  4. Ling Gong
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Correspondence to Yibo Wang.

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Wang, J., Yan, Y., Chen, J. et al. Novel FBN1 mutations are responsible for cardiovascular manifestations of Marfan syndrome. Mol Biol Rep 43, 1227–1232 (2016). https://doi.org/10.1007/s11033-016-4067-y

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