A novel deletion of BRCA1 gene that eliminates the ATG initiation codon without affecting the promoter region.
BACKGROUND
Point mutations in the highly penetrant cancer susceptibility gene BRCA1 are responsible for the majority of hereditary breast and/or ovarian cancer. We describe a novel large rearrangement of the BRCA1 gene identified in an Italian woman affected by an early onset bilateral breast cancer and a family history of hereditary breast cancer. The proband and her parents were negative for the presence of point mutations in BRCA1 and BRCA2 genes.


METHODS
Multiplex ligation-dependent probe amplification (MLPA) was used to detect rearrangements in the BRCA1 gene. The breakpoint of the rearrangement identified in the proband was defined by restriction mapping and PCR amplification. BRCA1 mRNA encoded by the mutant allele was isolated from peripheral blood.


RESULTS
The proband was heterozygous for a 9.1 kb deletion spanning from intron 1 to intron 3 (g.1238_10350del) that eliminates exons 2 and 3 in the mature mRNA. In mutant mRNA exon 1a joins directly to exon 5 with no disruption of the reading frame.


CONCLUSIONS
This deletion that eliminates the ATG initiation site in exon 2 and the sequence located in exons 2 and 3 encoding part of the RING finger domain of BRCA1 protein, is expected to abolish the function of this protein.
Marino
Marco
M
Department of Biomedical Sciences, University of Modena and Reggio Emilia, via Campi 287, I-41100 Modena, Italy. markkkus@tiscali.it
Rabacchi
Claudio
C
Simone
Maria Luisa
ML
Medici
Veronica
V
Cortesi
Laura
L
Calandra
Sebastiano
S
D000328:Adult; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics; D018387:Codon, Initiator / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D019398:Genes, BRCA1; D006579:Heterozygote; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D010375:Pedigree; D011401:Promoter Regions, Genetic / Q000235:genetics*
D018387:Codon, Initiator; D018076:DNA, Complementary