Title
An FBN1 deep intronic mutation in a familial case of Marfan syndrome : an explanation for genetically unsolved cases?An FBN1 deep intronic mutation in a familial case of Marfan syndrome : an explanation for genetically unsolved cases?
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Research group
Medical Genetics (MEDGEN)
Human molecular genetics
Publication type
article
Publication
New York, N.Y.,
Subject
Human medicine
Source (journal)
Human mutation. - New York, N.Y.
Volume/pages
35(2014):5, p. 571-574
ISSN
1059-7794
ISI
000334658800009
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Marfan syndrome (MFS) is caused by mutations in the FBN1 (fibrillin-1) gene, but approximately 10% of MFS cases remain genetically unsolved. Here, we report a new FBN1 mutation in an MFS family that had remained negative after extensive molecular genomic DNAFBN1 testing, including denaturing high-performance liquid chromatography, Sanger sequencing, and multiplex ligation-dependent probe amplification. Linkage analysis in the family and cDNA sequencing of the proband revealed a deep intronic point mutation in intron 56 generating a new splice donor site. This mutation results in the integration of a 90-bp pseudo-exon between exons 56 and 57 containing a stop codon, causing nonsense-mediated mRNA decay. Although more than 90% of FBN1 mutations can be identified with regular molecular testing at the genomic level, deep intronic mutations will be missed and require cDNA sequencing or whole-genome sequencing.
E-info
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