BRCA1-related malignancies in a family presenting with von Recklinghausen's disease.

BACKGROUND: The association between neurofibromatosis and gynecologic malignancies is rarely reported in the literature. Both BRCA1 and NF1 genes are located on the long arm of chromosome 17.

CASE: We have observed a pedigree showing several individuals affected by both type 1 neurofibromatosis (NF1) and breast or coelomatic cancers. The number of individuals affected, their degree of relationship, and the early age at onset were suggestive of an hereditary breast/ovarian cancer syndrome. Linkage analysis was performed in order to establish whether markers in the chromosome 17 region containing the BRCA1 and NF1 loci were shared by affected individuals. Screening for BRCA1 mutations was performed by PTT and SSCP. Analysis of chromosome 17 DNA markers in the five family members tested show that three individuals affected by both NF1 and carcinomas share a common haplotype including the NF1 and BRCA1 loci on chromosome 17. Mutation analysis showed the presence of a nonsense mutation within BRCA1 exon 12 in two individuals, mother and daughter, affected by breast and peritoneal cancer, respectively, as well as in the son, who had rectal cancer at the early age of 27 years. All three subjects also had NF1.

CONCLUSION: The concurrence of NF1 and hereditary breast/ovarian cancer in this family is likely due to the presence of two linked mutations at the NF1 and BRCA1 loci.