Format

Send to

Choose Destination
J Cyst Fibros. 2011 May;10(3):212-6. doi: 10.1016/j.jcf.2010.12.008. Epub 2011 Feb 12.

Splicing defects in the CFTR gene: minigene analysis of two mutations, 1811+1G>C and 1898+3A>G.

Author information

1
INSERM U613, Brest, France.

Abstract

BACKGROUND:

Cystic fibrosis is caused by mutations of the Cystic Fibrosis Transmembrane conductance Regulator gene (CFTR). Among the 1795 reported mutations, 221 (12.31%) are believed to affect pre-mRNA splicing. Nevertheless, not all splicing mutations have been demonstrated, by functional assays, to affect splicing in living cells.

METHODS:

We have used a minigene-based approach, coupled to site-specific mutagenesis, to analyze the effects of presumptive pre-mRNA splicing mutations.

RESULTS:

We show here that the intron 11 1811+1G>C and the intron 12 1898+3A>G mutations strongly affected CFTR pre-mRNA splicing. The encoded proteins are predicted to be defective, which would thus participate in the disease phenotype of carrier individuals.

CONCLUSIONS:

These results further validate the minigene strategy for the study of presumptive splice mutations, and report unanticipated defects in splicing. Such assays should improve the analysis of genotype-phenotype correlations.

PMID:
21317048
DOI:
10.1016/j.jcf.2010.12.008
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center