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Title
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An FBN1 deep intronic mutation in a familial case of Marfan syndrome : an explanation for genetically unsolved cases?
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Author
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Abstract
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| 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. |
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Language
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English
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Source (journal)
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Human mutation. - New York, N.Y.
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Publication
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New York, N.Y.
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2014
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ISSN
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1059-7794
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DOI
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10.1002/HUMU.22540
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Volume/pages
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35
:5
(2014)
, p. 571-574
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ISI
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000334658800009
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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