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A Novel Heterozygous Intronic Mutation in the FBN1 Gene Contributes to FBN1 RNA Missplicing Events in the Marfan Syndrome
Joint Authors
Torrado, Mario
Maneiro, Emilia
Trujillo-Quintero, Juan Pablo
Evangelista, Arturo
Monserrat, Lorenzo
Mikhailov, Alexander T.
Source
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-05-29
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
Marfan syndrome (MFS) is an autosomal dominantly inherited connective tissue disorder, mostly caused by mutations in the fibrillin-1 (FBN1) gene.
We, by using targeted next-generation sequence analysis, identified a novel intronic FBN1 mutation (the c.2678-15C>A variant) in a MFS patient with aortic dilatation.
The computational predictions showed that the heterozygous c.2678-15C>A intronic variant might influence the splicing process by differentially affecting canonical versus cryptic splice site utilization within intron 22 of the FBN1 gene.
RT-PCR and Western blot analyses, using FBN1 minigenes transfected into HeLa and COS-7 cells, revealed that the c.2678-15C>A variant disrupts normal splicing of intron 22 leading to aberrant 13-nt intron 22 inclusion, frameshift, and premature termination codon.
Collectively, the results strongly suggest that the c.2678-15C>A variant could lead to haploinsufficiency of the FBN1 functional protein and structural connective tissue fragility in MFS complicated by aorta dilation, a finding that further expands on the genetic basis of aortic pathology.
American Psychological Association (APA)
Torrado, Mario& Maneiro, Emilia& Trujillo-Quintero, Juan Pablo& Evangelista, Arturo& Mikhailov, Alexander T.& Monserrat, Lorenzo. 2018. A Novel Heterozygous Intronic Mutation in the FBN1 Gene Contributes to FBN1 RNA Missplicing Events in the Marfan Syndrome. BioMed Research International،Vol. 2018, no. 2018, pp.1-10.
https://search.emarefa.net/detail/BIM-1125895
Modern Language Association (MLA)
Torrado, Mario…[et al.]. A Novel Heterozygous Intronic Mutation in the FBN1 Gene Contributes to FBN1 RNA Missplicing Events in the Marfan Syndrome. BioMed Research International No. 2018 (2018), pp.1-10.
https://search.emarefa.net/detail/BIM-1125895
American Medical Association (AMA)
Torrado, Mario& Maneiro, Emilia& Trujillo-Quintero, Juan Pablo& Evangelista, Arturo& Mikhailov, Alexander T.& Monserrat, Lorenzo. A Novel Heterozygous Intronic Mutation in the FBN1 Gene Contributes to FBN1 RNA Missplicing Events in the Marfan Syndrome. BioMed Research International. 2018. Vol. 2018, no. 2018, pp.1-10.
https://search.emarefa.net/detail/BIM-1125895
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1125895