title: De novo recurrent germline mutation of the BRCA2 gene in a patient with early onset breast cancer.
abstract: Germline mutations in either of the two major breast cancer predisposition genes, BRCA1 and BRCA2, account for a significant proportion of hereditary breast/ovarian cancer. Identification of breast cancer patients carrying mutations of these genes is primarily based on a positive family history of breast/ovarian cancer or early onset of the disease or both. In the course of mutation screening of the BRCA1 and BRCA2 genes in a hospital based series of patients with risk factors for hereditary breast/ovarian cancer, we identified a germline mutation in the BRCA2 gene (3034del4) in a patient with early onset breast cancer and no strong family history of the disease. Subsequent molecular analysis in her parents showed that neither of them carried the mutation. Paternity was confirmed using a set of highly polymorphic markers, showing that the proband carried a de novo germline mutation in the BRCA2 gene. Interestingly, 3034del4 is a recurrent mutation occurring in a putative mutation prone region of the BRCA2 gene. Our study presents the first case in which a de novo germline mutation in the BRCA2 gene has been identified, and supports previous results of haplotype studies, confirming that the 3034del4 mutation has multiple independent origins.
authors.affiliation: Department of Medical Genetics, University Medical Centre Utrecht, KC.04.084.2, PO Box 85090, 3508 AB Utrecht, The Netherlands. r.b.vanderluijt@dmg.azu.nl
authors.forename: R B
authors.initials: RB
authors.lastname: van der Luijt
authors.forename: P H
authors.initials: PH
authors.lastname: van Zon
authors.forename: R P
authors.initials: RP
authors.lastname: Jansen
authors.forename: C J
authors.initials: CJ
authors.lastname: van der Sijs-Bos
authors.forename: C C
authors.initials: CC
authors.lastname: Wárlám-Rodenhuis
authors.forename: M G
authors.initials: MG
authors.lastname: Ausems
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D024682:BRCA2 Protein; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005192:Family Health; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D024682:BRCA2 Protein; D004273:DNA, Neoplasm; D005819:Genetic Markers; D009363:Neoplasm Proteins; D014157:Transcription Factors