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Author Torrado, Mario ♦ Maneiro, Emilia ♦ Trujillo-Quintero, Juan Pablo ♦ Evangelista, Arturo ♦ Mikhailov, Alexander T. ♦ Monserrat, Lorenzo
Editor Ono, Shoichiro
Source Hindawi
Content type Text
Publisher Hindawi
File Format PDF
Copyright Year ©2018
Language English
Abstract 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.
ISSN 23146133
Learning Resource Type Article
Publisher Date 2018-05-29
Rights License This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
e-ISSN 23146141
Journal BioMed Research International
Volume Number 2018
Page Count 10


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