心脏猝死(SCD)可能具有遗传性心脏病背景。基因检测支持死后诊断和筛查有风险的亲属。我们的目标是确定捷克国家合作小组的可行性,并确定分子尸检和家庭筛查的临床重要性。从2016年到2021年,我们评估了100例无关的SCD病例(71.0%为男性,年龄:33.3(12.8)岁)。利用一组100个与遗传性心脏/主动脉疾病和/或全外显子组测序相关的基因,通过下一代测序进行遗传测试。根据尸检,病例分为心肌病,心律失常猝死综合征,不明原因的猝死综合征,主动脉猝死.根据ACMG/AMP建议,我们在22/100(22.0%)的病例中发现了致病性/可能的致病性变异。由于DNA质量差,我们在受影响的亲属或健康父母中进行了间接DNA检测,诊断基因产量为11/24(45.8%)和1/10(10.0%),分别。心脏病和遗传筛查显示83/301(27.6%)亲属有SCD风险。在受影响的亲属中作为起始材料的基因测试导致高诊断产量,当没有合适的材料时提供有价值的替代方案。这是捷克共和国的第一个多学科/多中心分子尸检研究,支持建立这种诊断测试。中央协调员和各中心之间的适当沟通对于国家一级合作的成功至关重要。
Sudden cardiac death (SCD) might have an inherited cardiac condition background. Genetic testing supports post-mortem diagnosis and screening of relatives at risk. Our aim is to determine the feasibility of a Czech national collaboration group and to establish the clinical importance of molecular autopsy and family screening. From 2016 to 2021, we have evaluated 100 unrelated SCD cases (71.0% males, age: 33.3 (12.8) years). Genetic testing was performed by next-generation sequencing utilizing a panel of 100 genes related to inherited cardiac/aortic conditions and/or whole exome sequencing. According to autopsy, cases were divided into cardiomyopathies, sudden arrhythmic death syndrome, sudden unexplained death syndrome, and sudden aortic death. We identified pathogenic/likely pathogenic variants following ACMG/AMP recommendations in 22/100 (22.0%) of cases. Since poor DNA quality, we have performed indirect DNA testing in affected relatives or in healthy parents reaching a diagnostic genetic yield of 11/24 (45.8%) and 1/10 (10.0%), respectively. Cardiological and genetic screening disclose 83/301 (27.6%) relatives at risk of SCD. Genetic testing in affected relatives as starting material leads to a high diagnostic yield offering a valuable alternative when suitable material is not available. This is the first multidisciplinary/multicenter molecular autopsy
study in the Czech Republic which supports the establishment of this type of diagnostic tests. A central coordinator and proper communication among centers are crucial for the success of a collaboration at a national level.