遗传性心脏病中的大型新一代测序基因检测板：临床实践中的挑战
Large next-generation sequencing gene panels in genetic heart disease: challenges in clinical practice.
作者信息
Christiaans I, Mook O R F, Alders M, Bikker H, Lekanne Dit Deprez R H
机构信息
Department of Clinical Genetics, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Department of Clinical Genetics, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
出版信息
Neth Heart J. 2019 Jun;27(6):299-303. doi: 10.1007/s12471-019-1251-4.
BACKGROUND
Next-generation sequencing gene panels are increasingly used for genetic diagnosis in inherited cardiac diseases. Besides pathogenic variants, multiple variants, variants of uncertain significance (VUS) and incidental findings can be detected. Such test results can be challenging for counselling and clinical decision making.
METHODS
We present patient cases to illustrate the challenges that can arise when unclear genetic test results are detected in cardiogenetic gene panels.
RESULTS
We identified three types of challenging gene panel results: 1) one or more VUS in combination with a pathogenic variant, 2) variants associated with another genetic heart disease, and 3) variants associated with a syndrome involving cardiac features.
CONCLUSION
Large gene panels not only increase the detection rates of pathogenic variants but also of variants with uncertain pathogenicity, multiple variants and incidental findings. Gene panel results can be challenging for genetic counselling and require proper pre-test and post-test counselling. We advise evaluation of challenging cases by a multidisciplinary team.
背景
新一代测序基因检测板越来越多地用于遗传性心脏病的基因诊断。除了致病变异外，还可检测到多个变异、意义未明的变异（VUS）和偶发发现。这样的检测结果对于遗传咨询和临床决策可能具有挑战性。
方法
我们展示患者病例，以说明在心脏发生相关基因检测板中检测到不明确的基因检测结果时可能出现的挑战。
结果
我们确定了三种具有挑战性的基因检测板结果：1）一个或多个VUS与一个致病变异同时存在，2）与另一种遗传性心脏病相关的变异，3）与涉及心脏特征的综合征相关的变异。
结论
大型基因检测板不仅提高了致病变异的检出率，也提高了致病性不确定的变异、多个变异和偶发发现的检出率。基因检测板结果对于遗传咨询可能具有挑战性，需要进行适当的检测前和检测后咨询。我们建议由多学科团队对具有挑战性的病例进行评估。
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