Screening for the BRCA1-ins6kbEx13 mutation: potential for misdiagnosis. Mutation in brief #964. Online.
Screening for the BRCA1-ins6kbEx13 mutation: potential for misdiagnosis. Mutation in brief #964. Online.
复制标题
筛查 BRCA1-ins6kbEx13 突变：误诊的可能性。
DOI：
10.1002/humu.9493
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发表时间：
2007
期刊：
影响因子：
3.9
通讯作者：
Gayther,SimonA
中科院分区：
文献类型：
--
作者：
Ramus,SusanJ;Harrington,PatriciaA;Pye,Carole;Peock,Susan;Cook,MargaretR;Cox,MarkJ;Jacobs,IanJ;DiCioccio,RichardA;Whittemore,AliceS;Piver,MSteven;EMBRACE;Easton,DouglasF;Ponder,BruceAJ;Pharoah,PaulDP;Gayther,SimonA
与遗传性疾病综合征相关的生殖系突变的误诊可能对患者的临床管理产生严重影响。假阴性诊断（基因筛查遗漏的突变）限制了家庭内干预策略的决策。更严重的是假阳性诊断的后果（基因测试表明突变存在，而实际上并不存在）。这可能导致一个人被错误地诊断为突变携带者，接受不必要的临床干预，可能涉及降低风险的手术。作为筛选283个卵巢癌家族BRCA1突变的一部分，我们使用了两种不同的方法（突变特异性PCR和多重连接依赖性探针扩增）来筛选已知的重排突变L78833.1：g.44369_50449dup（ins6kbEx13）。我们在几个家庭中发现了假阳性和假阴性结果。然后，我们测试了61名来自BRCA1和BRCA2突变携带者流行病学研究（EMBRACE研究）的已知携带者或非携带者。这些数据强调了在解释ins6kbEx13突变和类似突变的分析时需要谨慎，其中表征有害突变的确切序列改变不是常规基因检测的一部分。© 2007 Wiley利斯公司
Misdiagnosis of a germline mutation associated with an inherited disease syndrome can have serious implications for the clinical management of patients. A false negative diagnosis (mutation missed by genetic screening) limits decision making about intervention strategies within families. More serious is the consequence of a false positive diagnosis (genetic test suggesting a mutation is present when it is not). This could lead to an individual, falsely diagnosed as a mutation carrier, undergoing unnecessary clinical intervention, possibly involving risk‐reducing surgery. As part of screening 283 ovarian cancer families for BRCA1 mutations, we used two different methods (mutation specific PCR and multiplex ligation‐dependant probe amplification) to screen for a known rearrangement mutation L78833.1:g.44369_50449dup (ins6kbEx13). We found false positive and false negative results in several families. We then tested 61 known carriers or non‐carriers from an epidemiological study of BRCA1 and BRCA2 mutation carriers (the EMBRACE study). These data highlight the need for caution when interpreting analyses of the ins6kbEx13 mutation and similar mutations, where characterising the exact sequence alteration for a deleterious mutation is not a part of the routine genetic test. © 2007 Wiley‐Liss, Inc.