Ahlborn, Lise B3; Steffensen, Ane Y1; Jønson, Lars1; Djursby, Malene2; Nielsen, Finn C1; Gerdes, Anne-Marie2; Hansen, Thomas V O1
1 Genomisk Medicinsk Enhed, Diagnostisk Center, Rigshospitalet, The Capital Region of Denmark2 Klinisk Genetisk Klinik, Juliane Marie Centre, Rigshospitalet, The Capital Region of Denmark3 unknown
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.
Familial Cancer, 2015, Vol 14, Issue 1, p. 129-133