Confirmation of BRCA1 by analysis of germline mutations linked to breast and ovarian cancer in ten families

Nat Genet. 1994 Dec;8(4):399-404. doi: 10.1038/ng1294-399.


We provide genetic evidence supporting the identity of the candidate gene for BRCA1 through the characterization of germline mutations in 63 breast cancer patients and 10 ovarian cancer patients in ten families with cancer linked to chromosome 17q21. Nine different mutations were detected by screening BRCA1 DNA and RNA by single-strand conformation polymorphism analysis and direct sequencing. Seven mutations lead to protein truncations at sites throughout the gene. One missense mutation (which occurred independently in two families) leads to loss of a cysteine in the zinc binding domain. An intronic single basepair substitution destroys an acceptor site and activates a cryptic splice site, leading to a 59 basepair insertion and chain termination. The four families with both breast and ovarian cancer had chain termination mutations in the N-terminal half of the protein.

Publication types

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

MeSH terms

  • BRCA1 Protein
  • Base Sequence
  • Breast Neoplasms / genetics*
  • DNA, Complementary
  • Female
  • Germ-Line Mutation*
  • Humans
  • Male
  • Molecular Sequence Data
  • Neoplasm Proteins / genetics*
  • Ovarian Neoplasms / genetics*
  • Pedigree
  • Polymorphism, Genetic
  • Transcription Factors / genetics*


  • BRCA1 Protein
  • DNA, Complementary
  • Neoplasm Proteins
  • Transcription Factors