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The variants BRCA1 IVS6-1G>A and BRCA2 IVS15+1G>A lead to aberrant splicing of the transcripts

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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.

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Authors and Affiliations

  1. Fundació Institut de Recerca de l’Hospital Universitari Vall d’Hebron, Barcelona, Spain

    Sara Gutiérrez-Enríquez, Miriam Masas & Orland Diez

  2. Laboratori de Biologia Molecular, Laboratoris Clinics, Soterrani de l’Hospital Materno Infantil Vall d’Hebron, Passeig de la Vall d’Hebron 119-129, 08035, Barcelona, Spain

    Sara Gutiérrez-Enríquez

  3. Facultat de Biociències, Universitat Autònoma de Barcelona, Barcelona, Spain

    Verònica Coderch

  4. Unitat d’Alt Risc i Prevenció del Càncer, Hospital Universitari Vall d’Hebron, Barcelona, Spain

    Judith Balmaña

  5. Programa de Medicina Molecular i Genètica, Hospital Universitari Vall d’Hebron, Barcelona, Spain

    Orland Diez

Authors
  1. Sara Gutiérrez-Enríquez
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  2. Verònica Coderch
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  3. Miriam Masas
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  4. Judith Balmaña
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  5. Orland Diez
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Corresponding author

Correspondence to Sara Gutiérrez-Enríquez.

Additional information

An RNA analysis published online recently, showed that the BRCA2 IVS15+2T>G caused skipping of exon 15 in RNA isolated from skin fibroblasts [Vreeswijk MPG, Kraan JN, van der Klift HM et al (2008) Intronic variants in BRCA1 and BRCA2 that affect RNA splicing can be reliably selected by splice-site prediction programs. Hum Mutat Published Online. doi:10.1002/humu.20811].

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Gutiérrez-Enríquez, S., Coderch, V., Masas, M. et al. The variants BRCA1 IVS6-1G>A and BRCA2 IVS15+1G>A lead to aberrant splicing of the transcripts. Breast Cancer Res Treat 117, 461–465 (2009). https://doi.org/10.1007/s10549-008-0154-7

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  • DOI: https://doi.org/10.1007/s10549-008-0154-7

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