RT Journal Article
T1 Large Genomic Rearrangements of BRCA1 and BRCA2 among Patients Referred for Genetic Analysis in Galicia (NW Spain): Delimitation and Mechanism of Three Novel BRCA1 Rearrangements
A1 Fachal Vilar, Laura
A1 Blanco Pérez, Ana
A1 Santamariña Pena, Marta
A1 Carracedo Álvarez, Ángel
A1 Vega Gliemmo, Ana Paula
AB In the Iberian Peninsula, which includes mainly Spain and Portugal, large genomic rearrangements (LGRs) of BRCA1 andBRCA2 have respectively been found in up to 2.33% and 8.4% of families with hereditary breast and/or ovarian cancer(HBOC) that lack point mutations and small indels. In Galicia (Northwest Spain), the spectrum and frequency of BRCA1/BRCA2 point mutations differs from the rest of the Iberian populations. However, to date there are no Galician frequencyreports of BRCA1/BRCA2 LGRs. Here we used multiplex ligation-dependent probe amplification (MLPA) to screen 651Galician index cases (out of the 830 individuals referred for genetic analysis) without point mutations or small indels. Weidentified three different BRCA1 LGRs in four families. Two of them have been previously classified as pathogenic LGRs: thecomplete deletion of BRCA1 (identified in two unrelated families) and the deletion of exons 1 to 13. We also identified theduplication of exons 1 and 2 that is a LGR with unknown pathogenicity. Determination of the breakpoints of the BRCA1LGRs using CNV/SNP arrays and sequencing identified them as NG_005905.2:g.70536_180359del,NG_005905.2:g.90012_97270dup, and NC_000017.10:g.41230935_41399840delinsAluSx1, respectively; previous observations of BRCA1 exon1-24del, exon1-2dup, and exon1-13del LGRs have not characterized them in such detail. All the BRCA1LGRs arose from unequal homologous recombination events involving Alu elements. We also detected, by sequencing, oneBRCA2 LGR, the Portuguese founder mutation c.156_157insAluYa5. The low frequency of BRCA1 LGRs within BRCA1mutation carriers in Galicia (2.34%, 95% CI: 0.61–7.22) seems to differ from the Spanish population (9.93%, 95% CI: 6.76–14.27, P-value = 0.013) and from the rest of the Iberian population (9.76%, 95% CI: 6.69–13.94, P-value = 0.014).
PB PLOS
YR 2014
FD 2014
LK http://hdl.handle.net/10347/21807
UL http://hdl.handle.net/10347/21807
LA eng
NO Fachal L., Blanco A., Santamariña M., Carracedo A., Vega A. (2014). Large Genomic Rearrangements of BRCA1 and BRCA2 among Patients Referred for Genetic Analysis in Galicia (NW Spain): Delimitation and Mechanism of Three Novel BRCA1 Rearrangements. PLoS ONE 9(3): e93306
NO This work was supported by grants to AV from the Xunta de Galicia (10 PXIB 9101 297 PR) and the Fundación Mutua Madrileña. LF is supported by the Isabel Barreto programme of the Xunta de Galicia and the European Social Fund
DS Minerva
RD 27 abr 2026