Haplotype and phenotype analysis of six recurrent BRCA1 mutations in 61 families: Results of an international study

Susan L. Neuhausen, Sylvie Mazoyer, Lori Friedman, Michael Stratton, Ken Offit, Adelaide Caligo, Gail Tomlinson, Lisa Cannon-Albright, Tim Bishop, David Kelsell, Ellen Solomon, Barbara Weber, Fergus Couch, Jeffery Struewing, Patricia Tonin, Francine Durocher, Steven Narod, Mark H. Skolnick, Gilbert Lenoir, Olga SerovaBruce Ponder, Dominique Stoppa-Lyonnet, Douglas Easton, Mary Claire King, David E. Goldgar

Research output: Contribution to journalArticlepeer-review

231 Scopus citations


Several BRCA1 mutations have now been found to occur in geographically diverse breast and ovarian cancer families. To investigate mutation origin and mutation-specific phenotypes due to BRCA1, we constructed a haplotype of nine polymorphic markers within or immediately flanking the BRCA1 locus in a set of 61 breast/ovarian cancer families selected for having one of six recurrent BRCA1 mutations. Tests of both mutations and family-specific differences in age at diagnosis were not significant. A comparison of the six mutations in the relative proportions of cases of breast and ovarian cancer was suggestive of an effect (P = .069), with 57% of women presumed affected because of the 1294 del 40 BRCA1 mutation having ovarian cancer, compared with 14% of affected women with the splice-site mutation in intron 5 of BRCA1. For the BRCA1 mutations studied here, the individual mutations are estimated to have arisen 9-170 generations ago. In general, a high degree of haplotype conservation across the region was observed, with haplotype differences most often due to mutations in the short-tandem-repeat markers, although some likely instances of recombination also were observed. For several of the instances, there was evidence for multiple, independent, BRCA1 mutational events.

Original languageEnglish (US)
Pages (from-to)271-280
Number of pages10
JournalAmerican Journal of Human Genetics
Issue number2
StatePublished - 1996
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


Dive into the research topics of 'Haplotype and phenotype analysis of six recurrent BRCA1 mutations in 61 families: Results of an international study'. Together they form a unique fingerprint.

Cite this