title: A novel deletion of BRCA1 gene that eliminates the ATG initiation codon without affecting the promoter region.
abstract: 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.
authors.affiliation: Department of Biomedical Sciences, University of Modena and Reggio Emilia, via Campi 287, I-41100 Modena, Italy. markkkus@tiscali.it
authors.forename: Marco
authors.initials: M
authors.lastname: Marino
authors.forename: Claudio
authors.initials: C
authors.lastname: Rabacchi
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Simone
authors.forename: Veronica
authors.initials: V
authors.lastname: Medici
authors.forename: Laura
authors.initials: L
authors.lastname: Cortesi
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Calandra
mesh_terms: 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*
chemical_list: D018387:Codon, Initiator; D018076:DNA, Complementary