Fanconi Anemia (FA) is an autosomal recessive syndrome characterized by 
congenital abnormalities, progressive bone marrow failure, and susceptibility to 
cancer. FA has eight known complementation groups and is caused by mutations in 
at least seven genes. Biallelic BRCA2 mutations were shown recently to cause 
FA-D1. Monoallelic (heterozygous) BRCA2 mutations confer a high risk of breast 
cancer and are a major cause of familial breast cancer. To investigate whether 
heterozygous variants in other FA genes are high penetrance breast cancer 
susceptibility alleles, we screened germ-line DNA from 88 BRCA1/2-negative 
families, each with at least three cases of breast cancer, for mutations in 
FANCA, FANCC, FANCD2, FANCE, FANCF, and FANCG. Sixty-nine sequence variants were 
identified of which 25 were exonic. None of the exonic variants resulted in 
translational frameshifts or nonsense codons and 14 were polymorphisms 
documented previously. Of the remaining 11 exonic variants, 2 resulted in 
synonymous changes, and 7 were present in controls. Only 2 conservative missense 
variants, 1 in FANCA and 1 in FANCE, were each found in a single family and were 
not present in 300 controls. The results indicate that FA gene mutations, other 
than in BRCA2, are unlikely to be a frequent cause of highly penetrant breast 
cancer predisposition.