The silent mutation nucleotide 744 G --> A, Lys172Lys, in exon 6 of BRCA2 results in exon skipping.
Germ-line mutations in BRCA2 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 BRCA2 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 BRCA2 silent mutation Lys172Lys is a disease-causing mutation.
Hansen
Thomas V O
TV
Department of Clinical Biochemistry 4111, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. tvoh@rh.dk
Steffensen
Ane Y
AY
Jønson
Lars
L
Andersen
Mette K
MK
Ejlertsen
Bent
B
Nielsen
Finn C
FC
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D018567:Breast Neoplasms, Male / Q000235:genetics; D002851:Chromatography, High Pressure Liquid; D005091:Exons / Q000235:genetics; D005260:Female; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics; D010375:Pedigree; D020133:Reverse Transcriptase Polymerase Chain Reaction