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Identification of Novel Causal FBN1 Mutations in Pedigrees of Marfan Syndrome.

ABSTRACT: Marfan syndrome (MFS) is an autosomal dominant genetic disorder of the connective tissue, typically characteristic of cardiovascular manifestations, valve prolapse, left ventricle enlargement, and cardiac failure. Fibrillin-1 (FBN1) is the causative gene in the pathogenesis of MFS. Patients with different FBN1 mutations often present more considerable phenotypic variation. In the present study, three affected MFS pedigrees were collected for genetic analysis. Using next-generation sequencing (NGS) technologies, 3 novel frameshift pathogenic mutations which are cosegregated with affected subjects in 3 pedigrees were identified. These novel mutations provide important diagnostic and therapeutic insights for precision medicine in MFS, especially regarding the lethal cardiovascular events.

SUBMITTER: Wang Y

PROVIDER: S-EPMC5932419 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Identification of Novel Causal FBN1 Mutations in Pedigrees of Marfan Syndrome.

Wang Yueli Y Li Xiaoyan X Li Rongjuan R Yang Ya Y Du Jie J

International journal of genomics 20180417

Marfan syndrome (MFS) is an autosomal dominant genetic disorder of the connective tissue, typically characteristic of cardiovascular manifestations, valve prolapse, left ventricle enlargement, and cardiac failure. Fibrillin-1 (FBN1) is the causative gene in the pathogenesis of MFS. Patients with different FBN1 mutations often present more considerable phenotypic variation. In the present study, three affected MFS pedigrees were collected for genetic analysis. Using next-generation ...[more]

PMID: 29850472

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Identification of a novel FBN1 gene mutation in a Chinese family with Marfan syndrome.

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| S-EPMC7057098 | biostudies-literature

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

Project description: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 ? 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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