Next-generation sequencing identifies novel mutations in the FBN1 gene for two Chinese families with Marfan syndrome

Ma,Mingjia; Li,Zongzhe; Wang,Dao Wen; Wei,Xiang

doi:10.3892/mmr.2016.5229

Next-generation sequencing identifies novel mutations in the FBN1 gene for two Chinese families with Marfan syndrome

Authors:
- Mingjia Ma
- Zongzhe Li
- Dao Wen Wang
- Xiang Wei
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Affiliations: Division of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China, Division of Cardiology, Department of Internal Medicine and the Genetic Diagnosis Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
Published online on: May 9, 2016 https://doi.org/10.3892/mmr.2016.5229
Pages: 151-158
Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Marfan syndrome (MFS) is an autosomal dominant heterogeneous disorder of connective tissue characterized by the early development of thoracic aneurysms/dissections, together with defects of the ocular and skeletal systems. Loss-of-function mutations in fibrillin-1 (FBN1) encoded by the gene, FBN1 (MFS‑1), and in the transforming growth factor β receptor 2 (TGFBR2) gene, TGFBR2 (MFS‑2), are major causes of this disorder. In the present study, a rapid and cost‑effective method for genetically diagnosing MFS was described and used to identify disease‑causing mutations in two unrelated pedigrees with MFS in mainland China. Using targeted semiconductor sequencing, two pathogenic mutations in four MFS patients of the two pedigrees were identified, including a novel frameshift insertion, p.G2120fsX2160, and a reported nonsense mutation, p.Arg529X (rs137854476), in the FBN1 gene. In addition, a rare, probably benign Chinese‑specific polymorphism in the FBN1 gene was also revealed.

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