title: The variants BRCA1 IVS6-1G>A and BRCA2 IVS15+1G>A lead to aberrant splicing of the transcripts.
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.
authors: Fundació Institut de Recerca de l'Hospital Universitari Vall d'Hebron, Barcelona, Spain. sagutier@vhebron.net
authors: Sara
authors: S
authors: Gutiérrez-Enríquez
authors: Verònica
authors: V
authors: Coderch
authors: Miriam
authors: M
authors: Masas
authors: Judith
authors: J
authors: Balmaña
authors: Orland
authors: O
authors: Diez
mesh_terms: D000328:Adult; D017398:Alternative Splicing / Q000235:genetics*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000235:genetics; D010375:Pedigree; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013030:Spain
chemical_list: D012333:RNA, Messenger