Garvin A M, Attenhofer-Haner M, Scott R J
Department of Research, Kantonsspital Basel, Switzerland.
J Med Genet. 1997 Dec;34(12):990-5. doi: 10.1136/jmg.34.12.990.
Eighty-six women fulfilling specific selection criteria were studied for germline mutations in two breast cancer susceptibility genes, BRCA1 and BRCA2, using the protein truncation test (PTT). Nine germline mutations were identified, six in BRCA1 and three in BRCA2. Of the six BRCA1 mutations, three have previously been described and three are new, and for BRCA2, one is a new mutation and the other two appear to occur at a site that has been described several times. Four kindreds were breast cancer families, one a breast/ovarian cancer family, and the sixth an ovarian cancer family. The three kindreds with BRCA2 mutations were classified as one breast/ovarian cancer family, one breast cancer family, and one family which harboured one early onset breast cancer patient and two melanoma patients. The mutations in BRCA1 were either insertions, deletions, or transitions which all resulted in a premature stop codon. Mutations in BRCA2 were all frameshift mutations as a result of either 2 or 4 bp deletions. Two BRCA2 mutations were identical, suggesting a Swiss founder effect which was confirmed by haplotype sharing. The 10% mutation detection rate is compatible with the relaxed criteria used for patient selection. Considering the relative ease with which coding sequences can be screened by PTT, this assay is useful as a first screen for BRCA1 and BRCA2 mutations.
采用蛋白质截短试验（PTT）对86名符合特定选择标准的女性进行了两个乳腺癌易感基因BRCA1和BRCA2的种系突变研究。共鉴定出9种种系突变，其中6种在BRCA1基因，3种在BRCA2基因。在这6种BRCA1突变中，3种先前已有描述，3种为新发现的突变；对于BRCA2基因，1种是新突变，另外2种似乎发生在一个已被多次描述的位点。4个家族为乳腺癌家族，1个为乳腺癌/卵巢癌家族，第6个为卵巢癌家族。携带BRCA2突变的3个家族被分类为1个乳腺癌/卵巢癌家族、1个乳腺癌家族以及1个有1例早发性乳腺癌患者和2例黑色素瘤患者的家族。BRCA1基因的突变包括插入、缺失或转换，均导致过早出现终止密码子。BRCA2基因的突变均为移码突变，由2个或4个碱基对的缺失引起。有2种BRCA2突变相同，提示存在瑞士始祖效应，单倍型共享证实了这一点。10%的突变检出率与用于患者选择的宽松标准相符。考虑到通过PTT筛选编码序列相对容易，该检测方法作为BRCA1和BRCA2突变的初步筛查很有用。
