A Novel Pathogenic BRCA1 Splicing Variant Produces Partial Intron Retention in the Mature Messenger RNA
AbstractAbout 10% of all breast cancers arise from hereditary mutations that increase the risk of breast and ovarian cancers; and about 25% of these are associated with the BRCA1 or BRCA2 genes. The identification of BRCA1/BRCA2 mutations can enable physicians to better tailor the clinical management of patients; and to initiate preventive measures in healthy carriers. The pathophysiological significance of newly identified variants poses challenges for genetic counseling. We characterized a new BRCA1 variant discovered in a breast cancer patient during BRCA1/2 screening by next-generation sequencing. Bioinformatic predictions; indicating that the variant is probably pathogenetic; were verified using retro-transcription of the patient’s RNA followed by PCR amplifications performed on the resulting cDNA. The variant causes the loss of a canonic donor splice site at position +2 in BRCA1 intron 21; and consequently the partial retention of 156 bp of intron 21 in the patient’s transcript; which demonstrates that this novel BRCA1 mutation plays a pathogenetic role in breast cancer. These findings enabled us to initiate appropriate counseling and to tailor the clinical management of this family. Lastly; these data reinforce the importance of studying the effects of sequence variants at the RNA level to verify their potential role in disease onset. View Full-Text
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Esposito, M.V.; Nunziato, M.; Starnone, F.; Telese, A.; Calabrese, A.; D’Aiuto, G.; Pucci, P.; D’Aiuto, M.; Baralle, F.; D’Argenio, V.; Salvatore, F. A Novel Pathogenic BRCA1 Splicing Variant Produces Partial Intron Retention in the Mature Messenger RNA. Int. J. Mol. Sci. 2016, 17, 2145.
Esposito MV, Nunziato M, Starnone F, Telese A, Calabrese A, D’Aiuto G, Pucci P, D’Aiuto M, Baralle F, D’Argenio V, Salvatore F. A Novel Pathogenic BRCA1 Splicing Variant Produces Partial Intron Retention in the Mature Messenger RNA. International Journal of Molecular Sciences. 2016; 17(12):2145.Chicago/Turabian Style
Esposito, Maria V.; Nunziato, Marcella; Starnone, Flavio; Telese, Antonella; Calabrese, Alessandra; D’Aiuto, Giuseppe; Pucci, Pietro; D’Aiuto, Massimiliano; Baralle, Francisco; D’Argenio, Valeria; Salvatore, Francesco. 2016. "A Novel Pathogenic BRCA1 Splicing Variant Produces Partial Intron Retention in the Mature Messenger RNA." Int. J. Mol. Sci. 17, no. 12: 2145.
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