The silent mutation nucleotide 744 G → A, Lys172Lys, in exon 6 of results in exon skipping

Thomas V. O. Hansen (1) , Ane Y. Steffensen (1) , Lars Jønson (1) , Mette K. Andersen (2) , Bent Ejlertsen (3) , Finn C. Nielsen (1)

1 Department of Clinical Biochemistry [Rigshospitalet]
2 Department of Clinical Genetics, The Juliane Marie Center
3 Department of Oncology

Germ-line mutations in predispose to breast and ovarian cancer. Mutations are widespread throughout the gene and include disease-causing mutations as frameshift, nonsense, splicing mutations and large genomic rearrangements. However a large number of mutations, including missense, silent and intron variants are of unknown significance. Here, we describe the functional characterization of a silent mutation (nucleotide 744 G → A/c.516 G → A, Lys172Lys) in exon 6 of in a Danish family with breast and ovarian cancer. Exon trapping analysis showed that the mutation results in skipping of exon 6 and/or both exon 5 and 6, which was verified by RT-PCR analysis on RNA isolated from whole blood of the affected patient. We therefore conclude that the silent mutation Lys172Lys is a disease-causing mutation.

Mots clés: Breast cancer; Silent mutation; Splicing; Exon trapping; RT-PCR

Thomas V. O. Hansen, Ane Y. Steffensen, Lars Jønson, Mette K. Andersen, Bent Ejlertsen, et al.. The silent mutation nucleotide 744 G → A, Lys172Lys, in exon 6 of results in exon skipping. Breast Cancer Research and Treatment, 2009, 119 (3), pp.547-550. ⟨10.1007/s10549-009-0359-4⟩. ⟨hal-00535346⟩