ClinGen--the Clinical Genome Resource.
ClinGen--the Clinical Genome Resource.
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DOI：
10.1056/nejmsr1406261
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发表时间：
2015-06-04
期刊：
影响因子：
--
通讯作者：
ClinGen
中科院分区：
文献类型：
--
作者：
Rehm HL;Berg JS;Brooks LD;Bustamante CD;Evans JP;Landrum MJ;Ledbetter DH;Maglott DR;Martin CL;Nussbaum RL;Plon SE;Ramos EM;Sherry ST;Watson MS;ClinGen
尸检时，发现患者患有肥厚型心肌病。患者的家人根据原始研究出版物中的一项研究进行基因检测，显示该疾病的“可能致病”变异。考虑到这种疾病的显性遗传和心脏性猝死的风险，其他家庭成员也会接受遗传变异的检测，以确定他们的风险。几个家庭成员的检测结果为阴性，并被告知他们没有患肥厚性心肌病和心源性猝死的风险，而那些检测结果为阳性的人则被告知他们需要定期接受超声心动图心肌病监测。五年后，在一个基因型阳性的家庭成员的常规诊所访问期间，心脏病专家查询了一个数据库，以了解有关遗传变异的当前知识，并发现该变异现在被另一个实验室解释为“可能是良性的”，该实验室使用最近获得的人群频率数据。一个新的可用的测试面板的额外的基因是牵连在肥厚型心肌病是开始对受影响的家庭成员，并发现一个不同的变体，被确定为致病性。家庭成员被重新测试，一个以前测试阴性的成员现在被发现对这种新的变体呈阳性。立即进行临床检查，发现心肌病的证据，并植入心内除颤器，以减少心脏猝死的风险。
On autopsy, a patient is found to have hypertrophic cardiomyopathy. The patient’s family pursues genetic testing that shows a “likely pathogenic” variant for the condition on the basis of a study in an original research publication. Given the dominant inheritance of the condition and the risk of sudden cardiac death, other family members are tested for the genetic variant to determine their risk. Several family members test negative and are told that they are not at risk for hypertrophic cardiomyopathy and sudden cardiac death, and those who test positive are told that they need to be regularly monitored for cardiomyopathy on echocardiography. Five years later, during a routine clinic visit of one of the genotype-positive family members, the cardiologist queries a database for current knowledge on the genetic variant and discovers that the variant is now interpreted as “likely benign” by another laboratory that uses more recently derived population-frequency data. A newly available testing panel for additional genes that are implicated in hypertrophic cardiomyopathy is initiated on an affected family member, and a different variant is found that is determined to be pathogenic. Family members are retested, and one member who previously tested negative is now found to be positive for this new variant. An immediate clinical workup detects evidence of cardiomyopathy, and an intracardiac defibrillator is implanted to reduce the risk of sudden cardiac death.