Osorio A, Robledo M, Martínez B, Cebrián A, San Román J M, Albertos J, Lobo F, Benítez J
Department of Genetics, Fundación Jiménez Díaz, Madrid, Spain.
Clin Genet. 1998 Aug;54(2):142-7. doi: 10.1111/j.1399-0004.1998.tb03717.x.
The recent isolated gene BRCA2 is responsible for about 45% of familial breast cancer and the majority of male breast cancer families. In order to evaluate the role of inherited BRCA2 mutations in Spanish families, the complete coding sequence of the gene was screened by SSCP/sequencing in 16 high-risk breast/ovarian cancer families. Four mutations were found that cause a premature termination codon. Two of them have been reported elsewhere and one is a novel mutation. In addition we have found seven polymorphisms, two of which have not been previously described. One of the mutations, 936delAAAC was found in two of our high-risk families. Because this mutation is considered as recurrent, we have tried to estimate its frequency in our breast cancer population. A total of 127 moderate- high-risk families were screened for this mutation and it was also found in another high-risk family. All the families carrying the 936delAAAC mutation harboured part of a common haplotype shared by other reported carriers, suggesting a possible founder effect for this mutation.
最近分离出的BRCA2基因约占家族性乳腺癌的45%，且在大多数男性乳腺癌家族中起作用。为了评估遗传性BRCA2突变在西班牙家族中的作用，我们通过单链构象多态性分析/测序技术对16个高危乳腺癌/卵巢癌家族的该基因完整编码序列进行了筛查。发现了4个导致提前终止密码子的突变。其中2个在其他地方已有报道，1个是新突变。此外，我们还发现了7个多态性位点，其中2个此前未被描述过。在我们的2个高危家族中发现了其中一个突变，即936delAAAC。由于该突变被认为是复发性的，我们试图估计其在我们乳腺癌人群中的频率。我们对总共127个中高危家族进行了该突变的筛查，并且在另一个高危家族中也发现了该突变。所有携带936delAAAC突变的家族都拥有其他已报道携带者所共有的部分单倍型，这表明该突变可能存在奠基者效应。
