A novel pathogenic BRCA1 splicing variant produces partial intron retention in the mature messenger RNA

Maria Valeria Esposito, Marcella Nunziato, Flavio Starnone, Antonella Telese, Alessandra Calabrese, Giuseppe D’Aiuto, Pietro Pucci, Massimiliano D'Aiuto, Francisco Baralle, Valeria D’Argenio, Francesco Salvatore

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

About 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.

Original languageEnglish
Article number2145
JournalInternational Journal of Molecular Sciences
Volume17
Issue number12
DOIs
Publication statusPublished - Dec 1 2016

Fingerprint

ribonucleic acids
splicing
RNA
breast
Introns
mutations
cancer
Breast Neoplasms
Messenger RNA
RNA Splice Sites
Transcription
Bioinformatics
Mutation
Amplification
Screening
Complementary DNA
Genes
BRCA2 Gene
BRCA1 Gene
physicians

Keywords

  • BRCA1
  • Breast cancer
  • Next generation sequencing
  • Partial intron retention
  • Splicing mutation

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Computer Science Applications
  • Spectroscopy
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

A novel pathogenic BRCA1 splicing variant produces partial intron retention in the mature messenger RNA. / Esposito, Maria Valeria; Nunziato, Marcella; Starnone, Flavio; Telese, Antonella; Calabrese, Alessandra; D’Aiuto, Giuseppe; Pucci, Pietro; D'Aiuto, Massimiliano; Baralle, Francisco; D’Argenio, Valeria; Salvatore, Francesco.

In: International Journal of Molecular Sciences, Vol. 17, No. 12, 2145, 01.12.2016.

Research output: Contribution to journalArticle

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 2016, 'A novel pathogenic BRCA1 splicing variant produces partial intron retention in the mature messenger RNA', International Journal of Molecular Sciences, vol. 17, no. 12, 2145. https://doi.org/10.3390/ijms17122145
Esposito, Maria Valeria ; Nunziato, Marcella ; Starnone, Flavio ; Telese, Antonella ; Calabrese, Alessandra ; D’Aiuto, Giuseppe ; Pucci, Pietro ; D'Aiuto, Massimiliano ; Baralle, Francisco ; D’Argenio, Valeria ; Salvatore, Francesco. / A novel pathogenic BRCA1 splicing variant produces partial intron retention in the mature messenger RNA. In: International Journal of Molecular Sciences. 2016 ; Vol. 17, No. 12.
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