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A Novel Pathogenic BRCA1 Splicing Variant Produces Partial Intron Retention in the Mature Messenger RNA

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 pat...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5187945/
https://www.ncbi.nlm.nih.gov/pubmed/28009814
http://dx.doi.org/10.3390/ijms17122145
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author 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
author_facet 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
author_sort Esposito, Maria Valeria
collection PubMed
description 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.
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spelling pubmed-51879452016-12-30 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 Int J Mol Sci Article 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. MDPI 2016-12-21 /pmc/articles/PMC5187945/ /pubmed/28009814 http://dx.doi.org/10.3390/ijms17122145 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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
title A Novel Pathogenic BRCA1 Splicing Variant Produces Partial Intron Retention in the Mature Messenger RNA
title_full A Novel Pathogenic BRCA1 Splicing Variant Produces Partial Intron Retention in the Mature Messenger RNA
title_fullStr A Novel Pathogenic BRCA1 Splicing Variant Produces Partial Intron Retention in the Mature Messenger RNA
title_full_unstemmed A Novel Pathogenic BRCA1 Splicing Variant Produces Partial Intron Retention in the Mature Messenger RNA
title_short A Novel Pathogenic BRCA1 Splicing Variant Produces Partial Intron Retention in the Mature Messenger RNA
title_sort novel pathogenic brca1 splicing variant produces partial intron retention in the mature messenger rna
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5187945/
https://www.ncbi.nlm.nih.gov/pubmed/28009814
http://dx.doi.org/10.3390/ijms17122145
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