Identification of a Danish breast/ovarian cancer family double heterozygote for BRCA1 and BRCA2 mutations

TY - JOUR

T1 - Identification of a Danish breast/ovarian cancer family double heterozygote for BRCA1 and BRCA2 mutations

AU - Steffensen, Ane Y

AU - Jønson, Lars

AU - Ejlertsen, Bent

AU - Gerdes, Anne-Marie

AU - Nielsen, Finn C

AU - Hansen, Thomas V O

PY - 2010/9/1

Y1 - 2010/9/1

N2 - 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.

AB - 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.

U2 - 10.1007/s10689-010-9345-6

DO - 10.1007/s10689-010-9345-6

M3 - Journal article

SN - 1389-9600

VL - 9

SP - 283

EP - 287

JO - Familial Cancer

JF - Familial Cancer

IS - 3

ER -