Intronic mutant of splice regulatory site causes a human afibrogenemia

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Jon Moulton
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Intronic mutant of splice regulatory site causes a human afibrogenemia

A mutation was found in intron 1 of the beta fibrinogen gene of a patient suffering afibrogenemia. A construct bearing the mutant of the fibrinogen beta gene was put into COS-7 cells. Using Endo-Porter to deliver a Morpholino into the cultured COS-7 cells corrected the mutant splicing to wild-type splicing. The Morpholino blocked the binding of a splice-regulatory protein to the mutant splice site.

Davis RL, Homer VM, George PM, Brennan SO. A deep intronic mutation in FGB creates a consensus exonic splicing enhancer motif that results in afibrinogenemia caused by aberrant mRNA splicing, which can be corrected in vitro with antisense oligonucleotide treatment. Hum Mutat. 2008 Oct 13. [Epub ahead of print]
http://www.ncbi.nlm.nih.gov/pubmed/18853456