Age-dependent penetrance of different germline mutations in the BRCA1 gene.
Age-dependent penetrance of different germline mutations in the BRCA1 gene.
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DOI：
10.1136/jcp.2008.062646
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发表时间：
2009-04
影响因子：
3.4
通讯作者：
Taylor GT
中科院分区：
文献类型：
--
作者：
Al-Mulla F;Bland JM;Serratt D;Miller J;Chu C;Taylor GT
BRCA 1基因突变与乳腺癌和卵巢癌易感性的关系已被广泛研究。各种基因型-表型相关性的尝试已经产生了关于BRCA 1突变后果的重要数据。然而，很少有人知道复发性BRCA突变对表达性和癌症发病年龄的影响。本研究探讨了不同的外显子突变是否具有不同的表达性，特别是与乳腺癌发病年龄有关。使用逐步系统的方法，最终在所有BRCA 1和BRCA 2外显子的测序，加上多重连接依赖的探针扩增，疾病表型和基因突变之间的关系，在219个人和他们的家庭成员进行了检查。研究表明，不同的BRCA 1基因突变对乳腺癌或卵巢癌的发病年龄有不同的影响。BRCA 1基因第2外显子的突变与第11、13和20外显子的突变相比，其突变率显著降低。乳腺癌患者的中位年龄为55岁（外显子2的185 delAG）（95%置信区间（CI）为46.7至59.5），47岁（95% CI为39至55.4），外显子11的4184 delTCAA突变（95% CI为39至55.4）和41岁（95% CI为32.9至49.7）BRCA 1基因的外显子13重复。此外，在约克郡/亨伯赛德郡人群中发现了14个BRCA 1和BRCA 2基因的新突变。结论：BRCA 1基因的185 delAG突变是一种低突变率突变，尤其是与外显子13重复突变相比，具有年龄依赖性。这些数据对BRCA 1基因突变携带者的筛查、遗传咨询和预防性治疗具有重要意义。
BRCA1 gene mutations have been extensively studied in relation to breast and ovarian cancer susceptibility. Various genotype–phenotype correlation attempts have yielded important data pertaining to the consequences of BRCA1 mutations. However, little is known about the effects of recurrent BRCA mutations on expressivity and the age of onset of cancer in a population. This study addresses whether different exon mutations have variable expressivity especially in relation to the age of onset of breast cancer. Using a step-wise systematic approach, culminating in the sequencing of all BRCA1 and BRCA2 exons with the addition of multiplex ligation-dependent probe amplification, the relationship between disease phenotypes and gene mutations in 219 individuals and their family members was examined. It is shown that different BRCA1 gene mutations have distinct effects that influence the age of onset of breast or ovarian cancer. Mutations in exon 2 of the BRCA1 gene had significantly lower penetrance compared with mutations of exons 11, 13 and 20. The median age of affliction with breast cancer was 55 years for 185delAG in exon 2 (95% confidence interval (CI) 46.7 to 59.5), 47 years for the 4184delTCAA mutation in exon 11 (95% CI 39 to 55.4), and 41 years for exon 13 duplication (95% CI 32.9 to 49.7) of the BRCA1 gene. Moreover, 14 novel mutations in BRCA1 and BRCA2 genes in the Yorkshire/Humberside population were identified. Conclusions: The 185delAG mutation of the BRCA1 gene is a low penetrance mutation that is age dependent especially when compared with the exon 13 duplication mutation. The data have important ramifications on screening, genetic counselling and prophylactic treatment of BRCA1 gene mutation carriers.
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影响因子：
6.4
作者：
Rashid, Muhammad U.;Zaidi, Anbreen;Hamann, Ute
通讯作者：
Hamann, Ute
影响因子：
3.9
作者：
Buisson, Monique;Anczukow, Olga;Mazoyer, Sylvie
通讯作者：
Mazoyer, Sylvie
影响因子：
254.7
作者：
Parkin, DM;Bray, F;Pisani, P
通讯作者：
Pisani, P
影响因子：
9.8
作者：
Kraft, P;Thomas, DC
通讯作者：
Thomas, DC
影响因子：
3.5
作者：
Perrin-Vidoz, L;Sinilnikova, OM;Mazoyer, S
通讯作者：
Mazoyer, S