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

Valeria Faa, Alessandra Coiana, Federica Incani, Lucy Costantino, Antonio Cao, Maria Cristina Rosatelli

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Abstract

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 nonfunctional 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, performed through DNA as well as RNA analyses, shows that this mutation creates a new 5′ splice site within exon 15, resulting in 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 open reading frame is in frame. This study indicates that apparently neutral polymorphism, which may be erroneously classified as nonpathogenic, may indeed led to aberrant splicing thereby resulting in defective protein.

Original languageEnglish
Pages (from-to)380-383
Number of pages4
JournalJournal of Molecular Diagnostics
Volume12
Issue number3
DOIs
Publication statusPublished - May 1 2010

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ASJC Scopus subject areas

  • Molecular Medicine
  • Pathology and Forensic Medicine

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