title: Next-generation sequencing identifies novel mutations in the FBN1 gene for two Chinese families with Marfan syndrome.
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.
authors.affiliation: Division of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Mingjia
authors.initials: M
authors.lastname: Ma
authors.affiliation: 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.
authors.forename: Zongzhe
authors.initials: Z
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Dao Wen
authors.initials: DW
authors.lastname: Wang
authors.affiliation: Division of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Wei
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D002675:Child, Preschool; D002681:China; D019295:Computational Biology / Q000379:methods; D004252:DNA Mutational Analysis; D004452:Echocardiography; D005260:Female; D000071838:Fibrillin-1 / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000175:diagnosis* / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D011247:Pregnancy; D014057:Tomography, X-Ray Computed
chemical_list: D000071838:Fibrillin-1