A nonsense mutation in the fibrillin-1 gene of a Marfan syndrome patient induces NMD and disrupts an exonic splicing enhancer

Massimo Caputi; Raymond J. Kendzior; Karen L. Beemon

doi:10.1101/gad.997502

A nonsense mutation in the fibrillin-1 gene of a Marfan syndrome patient induces NMD and disrupts an exonic splicing enhancer

Department of Biology, Johns Hopkins University, Baltimore, Maryland 21218, USA

Abstract

A nonsense mutation in the fibrillin-1 (FBN1) gene of a Marfan syndrome (MFS) patient induces in-frame exon skipping ofFBN1 exon 51. We present evidence, based on both in vivo and in vitro experiments, that the skipping of this exon is due to the disruption of an SC35-dependent splicing enhancer within exon 51. In addition, this nonsense mutation induces nonsense-mediated decay (NMD), which degrades the normally spliced mRNA in the patient's cells. In contrast to NMD, skipping of FBN1 exon 51 does not require translation.

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↵1 Corresponding author.
E-MAIL maxcaputi{at}earthlink.net; FAX (410) 516-7292.
Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.997502.
- Received April 9, 2002.
- Accepted May 24, 2002.
Cold Spring Harbor Laboratory Press