Use and interpretation of genetic tests in cardiovascular genetics
Use and interpretation of genetic tests in cardiovascular genetics
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DOI：
10.1136/hrt.2009.190090
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发表时间：
2010-10-01
期刊：
影响因子：
5.7
通讯作者：
Baxter, Samantha
中科院分区：
文献类型：
--
作者：
Caleshu, Colleen;Day, Sharlene;Baxter, Samantha
在过去的5到10年里，我们对许多孟德尔式心血管疾病的遗传基础的理解有了显著的进步。现在有许多专业协会指南建议对各种遗传性心血管疾病进行基因检测，包括长QT综合征，肥厚性心肌病和致心律失常性右心室心肌病（ARVC）。1 e3与心脏病相关的基因数量持续增加，近年来临床上可用的心脏病基因检测数量迅速扩大（表1）。临床基因检测在遗传性疾病家族的管理中具有很高的价值。确定哪些家庭成员遗传了心脏病的遗传易感性，使我们能够将那些需要终身临床评估的人与那些不需要进一步评估的人区分开来。这一策略在遗传性心血管疾病中特别有价值，因为在这些疾病中，对高危亲属的明确临床诊断受到不完全筛查、发病年龄可变以及在某些情况下临床检测不敏感的限制。4 e7最近的指导方针和专家意见已经超越了简单地推荐基因检测;他们强调了明智使用基因检测的要点，例如对家庭中最明显受影响的人进行基因检测，就阳性，阴性或不确定结果的影响进行仔细的遗传咨询，以及考虑转介到专业中心，因为这种遗传评估很复杂。1 8 9为了进一步阐明原则和方法的有效利用基因检测的关键，我们提出了四个案例，在心血管遗传学诊所和实验室，说明了适当使用和准确的解释基因tests.CASE 1的重要性评估一个33岁的妇女与临床诊断和家族史扩张型心肌病（DCM）提出的评价。病人对她的三个孩子表示担忧，他们都不到10岁。她在年轻时就失去了两个兄弟，死于心脏病猝死和对失去孩子的恐惧。临床医生提出了基因检测的实用性，并解释了她的测试结果如何用于确定她的孩子是否有患DCM的风险。患者同意进行基因检测，
Our understanding of the genetic basis of many Mendelian forms of cardiovascular disease has advanced significantly in the last 5e10 years. There are now many professional society guidelines that recommend genetic testing for a variety of hereditary cardiovascular diseases including long QTsyndrome, hypertrophic cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy (ARVC). 1e3 The number of genes associated with cardiac conditions continues to increase, and the number of clinically available genetic tests for cardiac conditions has expanded rapidly in recent years (table 1). Clinical genetic testing can be highly valuable in the management of families with hereditary disease. Determining which family members inherited the genetic predisposition to cardiac disease allows us to separate those in need of lifelong clinical evaluations from those who need no further evaluations beyond those recommended for the general population. This strategy is particularly valuable in inherited cardiovascular diseases where definitive clinical diagnosis of at-risk relatives is limited by incomplete penetrance, variable age of onset and, in some cases, insensitivity of clinical testing. 4e7 Recent guidelines and expert opinions have gone beyond simply recommending genetic testing; they emphasise important points for the judicious use of genetic testing such as performing genetic testing on the most clearly affected person in the family, careful genetic counselling regarding the implications of positive, negative or uncertain results, and consideration of referral to a specialised centre due to the complexity of such genetic evaluations. 1 8 9 To further elucidate principles and approaches critical to the effective use of genetic tests, we present four cases evaluated in cardiovascular genetics clinics and laboratories that illustrate the importance of appropriate use and accurate interpretation of genetic tests.CASE 1 A 33-year-old woman with a clinical diagnosis and family history of dilated cardiomyopathy (DCM) presents for evaluation. The patient brings up concerns about her three children, all under the age of 10 years. She lost two brothers at young ages to sudden cardiac death and fears for the loss of her children. The clinician brings up the utility of genetic testing, and explains how the results of her test could be used to determine whether or not her children are at risk for developing DCM. The patient consents to genetic testing and has