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 or genes. The identification of / mutations can enable physicians to better tailor the clinical management of patients; and to initiate...

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Bibliographic Details
Published in:International journal of molecular sciences 2016-12, Vol.17 (12), p.2145-2145
Main Authors: 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
Format: Article
Language:English
Subjects:
Adult
Aged
BRCA1
BRCA1 Protein - genetics
Breast cancer
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Female
Humans
Introns
Male
Mutation
next generation sequencing
partial intron retention
Pathogens
Pedigree
Ribonucleic acid
RNA
RNA Splicing
RNA, Messenger - genetics
RNA, Messenger - metabolism
splicing mutation
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Summary: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 or genes. The identification of / 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 variant discovered in a breast cancer patient during / 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 intron 21; and consequently the partial retention of 156 bp of intron 21 in the patient's transcript; which demonstrates that this novel 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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms17122145