Mutations in the BRCA1 gene in families with early-onset breast and ovarian cancer

Lucio H. Castilla, Fergus J. Couch, Michael R. Erdos, Kent F. Hoskins, Kathy Calzone, Judy E. Garber, Jeff Boyd, Matthew B. Lubin, Michelle L. Deshano, Lawrence C. Brody, Francis S. Collins, Barbara L. Weber

Research output: Contribution to journalArticlepeer-review

350 Scopus citations


We analysed 50 probands with a family history of breast and/or ovarian cancer for germline mutations in the coding region of the BRCA1 candidate gene, using single-strand conformation polymorphism (SSCP) analysis on PCR-amplified genomic DNA. A total of eight putative disease-causing alterations were identified: four of these are frameshifts and two are nonsense mutations. In addition, we found two missense mutations, one of which changes the final cysteine of the BRCA1 zinc finger motif to glycine. These data are consistent with a tumour suppressor model, and support the notion that this candidate gene is in fact BRCA1. The heterogeneity of mutations, coupled with the large size of the gene, indicates that clinical application of BRCA1 mutation testing will be technically challenging.

Original languageEnglish (US)
Pages (from-to)387-391
Number of pages5
JournalNature Genetics
Issue number4
StatePublished - Dec 1994

ASJC Scopus subject areas

  • Genetics


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