中文摘要：

目的：研究家族性和早发性乳腺癌BRCA1基因突变情况。方法：选取52例来自不同家系家族性和早发性乳腺癌患者，提取外周血基因组DNA，对BRCA1基因的全部编码序列及外显子与内含子的拼接区进行PCR基因扩增，扩增产物经变性高效液相色谱分析（DHPLC）除筛后，对发现异常的片断进行DNA直接测序证实。结果：在52例家族性和早发性乳腺癌患者中发现4例（7．7％）BRCA1致病性突变（2257C〉G，2229delAA，3413delT），其中BRCA1的2229delAA在两个不同的家系重复出现。3413delT突变未在BreastCancerInformationCore（BIC）数据库和相关的文献报道过。家族性乳腺癌突变率为12％（3／25）；单纯早发性乳腺癌突变率为3．7％（1／27）。结论：BRCA1突变在山东东部地区家族性乳腺癌的发病中发挥重要作用，对具有家族史的乳腺癌家系进行BRCA1基因突变筛查具有重要意义。

英文摘要：

Objective： To study the BRCA1 mutations in Chinese patients with early-onset breast cancer and in affected relatives. Methods： Fifty-two familial and/or early-onset breast cancer patients from unrelated family were analyzed. Genomic DNA was collected from the peripheral blood mononuclear cells, and the coding sequences and exon-intron boundaries of BRCA1 genes were screened by using denaturing high performance liquid chromatography （DHPLC）. Then the abnormal fragments were confirmed with direct DNA sequencing. Results： Three kinds of mutations in BRCA1 gene from four unrelated families were identified. They are 2257C〉G, 2229delAA, 3413delT and 2229delAA found in two unrelated families. 3413delT is a novel mutation that doesn＇t exist in Breast Cancer Information Core （BIC） database and was not reported before. Moreover, three mutations （12%） were identified in familial breast cancer patients, and one mutation （3.7%） in the early-onset breast cancer patients. Conclusions： BRCA1 may play an important role in the familial breast cancer in this population. It is necessary to give genetic test for familial breast cancer patients in this population.