title: The silent mutation nucleotide 744 G --> A, Lys172Lys, in exon 6 of BRCA2 results in exon skipping.
abstract: 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.
authors.affiliation: Department of Clinical Biochemistry 4111, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. tvoh@rh.dk
authors.forename: Thomas V O
authors.initials: TV
authors.lastname: Hansen
authors.forename: Ane Y
authors.initials: AY
authors.lastname: Steffensen
authors.forename: Lars
authors.initials: L
authors.lastname: Jønson
authors.forename: Mette K
authors.initials: MK
authors.lastname: Andersen
authors.forename: Bent
authors.initials: B
authors.lastname: Ejlertsen
authors.forename: Finn C
authors.initials: FC
authors.lastname: Nielsen
mesh_terms: 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