title: Identification of a breast cancer family double heterozygote for RAD51C and BRCA2 gene mutations.
abstract: Next-generation sequencing has entered routine genetic testing of hereditary breast cancer. It has provided the opportunity to screen multiple genes simultaneously, and consequently has identified new complex genotypes. Here we report the first identification of a woman double heterozygote for mutations in the RAD51C and BRCA2 genes. The RAD51C missense mutation p.Arg258His has previously been identified in a homozygous state in a patient with Fanconi anemia. This mutation is known to affect the DNA repair function of the RAD51C protein. The BRCA2 p.Leu3216Leu synonymous mutation has not been described before and mini-gene splicing experiments revealed that the mutation results in skipping of exon 26 containing a part of the DNA-binding domain. We conclude that the woman has two potential disease-causing mutations and that predictive testing of family members should include both the RAD51C and BRCA2 mutation. This study illustrates the advantage of sequencing gene panels using next-generation sequencing in terms of genetic testing.
authors.affiliation: Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark.
authors.forename: Lise B
authors.initials: LB
authors.lastname: Ahlborn
authors.forename: Ane Y
authors.initials: AY
authors.lastname: Steffensen
authors.forename: Lars
authors.initials: L
authors.lastname: Jønson
authors.forename: Malene
authors.initials: M
authors.lastname: Djursby
authors.forename: Finn C
authors.initials: FC
authors.lastname: Nielsen
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Gerdes
authors.forename: Thomas V O
authors.initials: TV
authors.lastname: Hansen
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006579:Heterozygote; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009154:Mutation; D010375:Pedigree
chemical_list: D004268:DNA-Binding Proteins; C448305:RAD51C protein, human