The variants BRCA1 IVS6-1G>A and BRCA2 IVS15+1G>A lead to aberrant splicing of the transcripts

Breast Cancer Res Treat. 2009 Sep;117(2):461-5. doi: 10.1007/s10549-008-0154-7. Epub 2008 Aug 19.

Abstract

The majority of BRCA1 and BRCA2 deleterious mutations and variants of unknown significance have been identified in genomic DNA and their effects at the mRNA level have not been reported. Our aim was to ascertain the pathological effect of the BRCA1 IVS6-1G>A (c. 302-1G>A) and the BRCA2 IVS15+1G>A (c. 7617+1G>A) variants detected in Spanish breast/ovarian cancer families. Sequencing of cDNA from the BRCA1 IVS6-1G>A allele revealed an inappropriate splicing of exon 7. The analysis of the BRCA2 IVS15+1G>A allele showed the skipping of exon 15. Both alterations predicted the appearance of premature stop codons. Our findings highlight the importance of studying mutations at DNA and RNA levels in order to clarify the effect of the suspected mutation and to provide adequate counseling for breast/ovarian cancer families.

MeSH terms

  • Adult
  • Alternative Splicing / genetics*
  • Base Sequence
  • Breast Neoplasms / genetics
  • Female
  • Genes, BRCA1*
  • Genes, BRCA2*
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Ovarian Neoplasms / genetics
  • Pedigree
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spain

Substances

  • RNA, Messenger