title: Identification of a Danish breast/ovarian cancer family double heterozygote for BRCA1 and BRCA2 mutations.
abstract: Mutations in the two breast cancer susceptibility genes BRCA1 and BRCA2 are associated with increased risk of breast and ovarian cancer. Patients with mutations in both genes are rarely reported and often involve Ashkenazi founder mutations. Here we report the first identification of a Danish breast and ovarian cancer family heterozygote for mutations in the BRCA1 and BRCA2 genes. The BRCA1 nucleotide 5215G > A/c.5096G > A mutation results in the missense mutation Arg1699Gln, while the BRCA2 nucleotide 859 + 4A > G/c.631 + 4A > G is novel. Exon trapping experiments and reverse transcriptase (RT)-PCR analysis revealed that the BRCA2 mutation results in skipping of exon 7, thereby introducing a frameshift and a premature stop codon. We therefore classify the mutation as disease causing. Since the BRCA1 Arg1699Gln mutation is also suggested to be disease-causing, we consider this family double heterozygote for BRCA1 and BRCA2 mutations.
authors.affiliation: Department of Clinical Biochemistry 4111, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark.
authors.forename: Ane Y
authors.initials: AY
authors.lastname: Steffensen
authors.forename: Lars
authors.initials: L
authors.lastname: Jønson
authors.forename: Bent
authors.initials: B
authors.lastname: Ejlertsen
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Gerdes
authors.forename: Finn C
authors.initials: FC
authors.lastname: Nielsen
authors.forename: Thomas V O
authors.initials: TV
authors.lastname: Hansen
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D018567:Breast Neoplasms, Male / Q000235:genetics; D003718:Denmark; D005190:Family; D005260:Female; D016368:Frameshift Mutation; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D010051:Ovarian Neoplasms / Q000235:genetics*; D010375:Pedigree; D020133:Reverse Transcriptase Polymerase Chain Reaction
references.citation: J Med Genet. 2002 Aug;39(8):e44
references.pmid: 12161611
references.citation: Breast Cancer Res Treat. 2009 May;115(1):69-76
references.pmid: 18500671
references.citation: Nucleic Acids Res. 2003 Jul 1;31(13):3812-4
references.pmid: 12824425
references.citation: J Clin Oncol. 2002 Mar 15;20(6):1480-90
references.pmid: 11896095
references.citation: Cancer Res. 2002 May 15;62(10):2741-3
references.pmid: 12019146
references.citation: Breast Cancer Res Treat. 2009 May;115(2):315-23
references.pmid: 18546071
references.citation: Am J Hum Genet. 1998 Oct;63(4):1224-7
references.pmid: 9758598
references.citation: Nucleic Acids Res. 1996 Sep 1;24(17):3439-52
references.pmid: 8811101
references.citation: Am J Hum Genet. 2004 Oct;75(4):535-44
references.pmid: 15290653
references.citation: Breast Cancer Res. 2009;11(1):R8
references.pmid: 19200354
references.citation: Breast Cancer Res. 2007;9(6):R82
references.pmid: 18036263
references.citation: Biochem Cell Biol. 2005 Dec;83(6):721-7
references.pmid: 16333323
references.citation: Nat Genet. 1996 May;13(1):126-8
references.pmid: 8673092
references.citation: J Comput Biol. 2004;11(2-3):377-94
references.pmid: 15285897
references.citation: Hum Mol Genet. 2001 Feb 15;10(4):353-60
references.pmid: 11157798
references.citation: Bioinformatics. 2005 Jul 15;21(14):3176-8
references.pmid: 15879453
references.citation: Cancer Res. 2006 Feb 15;66(4):2019-27
references.pmid: 16489001
references.citation: J Hum Genet. 2000;45(6):351-7
references.pmid: 11185744
references.citation: BMC Med Genet. 2008 Jul 02;9:58
references.pmid: 18597679
references.citation: Ann Oncol. 2009 May;20(5):874-8
references.pmid: 19179552
references.citation: Breast Cancer Res Treat. 2010 Feb;119(3):547-50
references.pmid: 19267246
references.citation: Fam Cancer. 2006;5(1):89-93
references.pmid: 16528612
references.citation: Nat Genet. 1996 May;13(1):117-9
references.pmid: 8673089
references.citation: Nucleic Acids Res. 2002 Sep 1;30(17):3894-900
references.pmid: 12202775
references.citation: J Med Genet. 2005 Oct;42(10):737-48
references.pmid: 16199547
references.citation: J Comput Biol. 1997 Fall;4(3):311-23
references.pmid: 9278062
references.citation: Acta Oncol. 2008;47(4):772-7
references.pmid: 18465347
references.citation: J Clin Oncol. 2004 May 1;22(9):1638-45
references.pmid: 15117986
references.citation: J Clin Oncol. 2008 Sep 1;26(25):4212-4; author reply 4214-5
references.pmid: 18757339
references.citation: J Med Genet. 2004 Jul;41(7):492-507
references.pmid: 15235020
references.citation: Nat Med. 2001 May;7(5):552-6
references.pmid: 11329055
references.citation: Nat Struct Mol Biol. 2004 Jun;11(6):512-8
references.pmid: 15133502
references.citation: J Med Genet. 2005 Mar;42(3):e20
references.pmid: 15744030
references.citation: Fam Cancer. 2008;7(2):119-24
references.pmid: 17636421