A high incidence of BRCA1 mutations in 20 breast-ovarian cancer families

Am J Hum Genet. 1996 Jan;58(1):42-51.


We have analyzed 20 breast-ovarian cancer families, the majority of which show positive evidence of linkage to chromosome 17q12 for germ-line mutations in the BRCA1 gene. BRCA1 mutations cosegregating with breast and ovarian cancer susceptibility were identified in 16 families, including 1 family with a case of male breast cancer. Nine of these mutations have not been reported previously. The majority of mutations were found to generate a premature stop codon leading to the formation of a truncated BRCA1 protein of 2%-88% of the expected normal length. Two mutations altered the RING finger domain. Sequencing of genomic DNA led to the identification of a mutation in the coding region of BRCA1 in 12 families, and cDNA analysis revealed an abnormal or missing BRCA1 transcript in 4 of the 8 remaining families. A total of eight mutations were associated with a reduced quantity of BRCA1 transcript. We were unable to detect BRCA1 mutations in 4 of the 20 families, but only 1 of these was clearly linked to BRCA1. It is expected that the majority of clear examples of the breast-ovarian syndrome will be associated with germ-line mutations in the coding region of BRCA1.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alternative Splicing
  • BRCA1 Protein
  • Breast Neoplasms / genetics*
  • Chromosome Mapping
  • Chromosomes, Human, Pair 17*
  • Codon
  • Exons
  • Female
  • Frameshift Mutation
  • Genetic Counseling
  • Genetic Linkage
  • Genotype
  • Humans
  • Male
  • Mutation*
  • Neoplasm Proteins / genetics*
  • Ovarian Neoplasms / genetics*
  • Pedigree
  • Phenotype
  • Polymorphism, Single-Stranded Conformational
  • Syndrome
  • Transcription Factors / genetics*


  • BRCA1 Protein
  • Codon
  • Neoplasm Proteins
  • Transcription Factors