Nordling M, Karlsson P, Wahlström J, Engwall Y, Wallgren A, Martinsson T
Department of Clinical Genetics, Sahlgrenska University Hospital, Gothenburg University, Sweden.
Cancer Res. 1998 Apr 1;58(7):1372-5.
We describe the identification of a large deletion in the BRCA2 gene as the disease-causing mutation in a Swedish breast/ovarian cancer family. The 5068-bp deletion encompassed the 3' region of exon 3, including the 3' splice site and most of intron 3, and it resulted on the mRNA level in an inframe exon 3 skipping. The junction site also included an insertion of 4 bp (CCAT). The mutation (nt504del5068insCCAT) resulted in a genotype absent of the two transcription activation regions localized to exon 3. The breast cancer phenotype associated with the described mutation resembled the phenotype of breast cancer found in both BRCA1 and BRCA2 mutation carriers. This is the first report of a large deletion as the disease-causing mutation in the BRCA2 gene.
我们描述了在一个瑞典乳腺癌/卵巢癌家族中，鉴定出BRCA2基因的一个大片段缺失为致病突变。这个5068bp的缺失涵盖了外显子3的3'区域，包括3'剪接位点和大部分内含子3，在mRNA水平上导致了外显子3的框内跳跃。连接位点还包括一个4bp（CCAT）的插入。该突变（nt504del5068insCCAT）导致外显子3中两个转录激活区域的基因型缺失。与所描述的突变相关的乳腺癌表型类似于在BRCA1和BRCA2突变携带者中发现的乳腺癌表型。这是关于BRCA2基因中大片段缺失作为致病突变的首次报道。
