A synonymous mutation in the CFTR gene causes an aberrant splicing in an Italian patient affected by a mild form of cystic fibrosis.

Mutations within exons are responsible for aberrant splicing of pre-mRNA in several human disease genes and in some viral systems. Nonsense, missense, and even synonymous mutations can induce aberrant skipping of the mutant exon producing non functional proteins. In this paper we describe the effect on the splicing efficiency of the synonymous variant 2811 G>T [Gly893Gly] detected in a patient of Italian descent affected by a mild form of Cystic Fibrosis, until now mentioned as sequence variation with unknown functional consequences. The study, carried out through DNA as well as RNA analysis, shows that this mutation creates a new 5' splice site within exon 15 causing a transcript lacking 76 amino acid residues. Although this aberrant splicing causes a shorter exon 15, the downstream exonic sequence from exon 16 to the end of the ORF is in frame. This study indicates that apparently neutral polymorphism, which may be erroneously classified as non-pathogenic, may indeed led to aberrant splicing thereby resulting in defective protein.