title: Germline mutations in NF1 and BRCA1 in a family with neurofibromatosis type 1 and early-onset breast cancer.
abstract: Neurofibromatosis type 1 (NF1) is a common dominant autosomal disorder caused by mutations in the NF1 gene. The main manifestations of NF1 are café-au-lait spots, neurofibromas, intertriginous freckling, Lisch nodules, and malignancy, including peripheral nerve sheath tumors, central nervous system gliomas, and a variety of other tumors not so clearly defined. The association between NF1 and breast cancer or other gynecologic malignancies seems uncommon and has been scarcely referred in the literature. We describe a family with two females affected by both NF1 and early-onset breast cancer, and a male with NF1. We evaluated whether the concomitance of both disorders could be attributed to a NF1 mutation and its supposed increased risk of breast cancer or to the concurrence of two NF1 and BRCA1/2 germline mutations. Mutation analyses identified a frameshift mutation in BRCA1 and a nonsense mutation in NF1. Our findings stress the importance of considering all phenotypic features in families with both NF1 and breast tumors. To offer a specific risk assessment and management of both conditions, NF1 and BRCA1/2 cancer predisposing genes should be analyzed.
authors.affiliation: Center for Molecular Genetic Diagnosis (CDGM)-IDIBELL, Gran Via de l'Hospitalet, 199, 08908, L'Hospitalet de Llobregat, Spain. bcampos@idibell.cat
authors.forename: Berta
authors.initials: B
authors.lastname: Campos
authors.forename: Judith
authors.initials: J
authors.lastname: Balmaña
authors.forename: Josep
authors.initials: J
authors.lastname: Gardenyes
authors.forename: Irene
authors.initials: I
authors.lastname: Valenzuela
authors.forename: Oscar
authors.initials: O
authors.lastname: Abad
authors.forename: Pere
authors.initials: P
authors.lastname: Fàbregas
authors.forename: Víctor
authors.initials: V
authors.lastname: Volpini
authors.forename: Orland
authors.initials: O
authors.lastname: Díez
mesh_terms: D000328:Adult; D017668:Age of Onset; D001943:Breast Neoplasms / Q000150:complications* / Q000175:diagnosis / Q000235:genetics*; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D005260:Female; D019398:Genes, BRCA1; D016514:Genes, Neurofibromatosis 1; D018095:Germ-Line Mutation; D006239:Haplotypes; D006801:Humans; D008297:Male; D009456:Neurofibromatosis 1 / Q000150:complications* / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree