Department of Cardiology, University Medical Centre, Utrecht, The Netherlands; Department of Internal Medicine and Cardiology, Bergman Clinics, Bilthoven, The Netherlands,.
Department of Clinical Genetics, University Medical Centre, Utrecht, The Netherlands.
Heart Rhythm. 2017 Jul;14(7):1035-1040. doi: 10.1016/j.hrthm.2017.01.010. Epub 2017 Jan 11.
Idiopathic ventricular fibrillation (IVF) is a rare primary cardiac arrhythmia syndrome that is diagnosed in a resuscitated cardiac arrest victim, with documented ventricular fibrillation, in whom no underlying cause is identified after comprehensive clinical evaluation. In some patients, causative genetic mutations are detected that facilitate patient treatment and follow-up. The feasibility of next-generation sequencing (NGS) has increased with its greater availability and decreasing costs.
The aim of this study was to assess the diagnostic yield of NGS in patients with IVF.
A total of 33 patients initially diagnosed with IVF were included (mean age 53 ± 15 years; 14(42%) men). In all included patients, NGS of 33 genes and the DPP6 haplotype revealed no pathogenic mutations. Genetic screening comprised NGS of a panel of 179 additional genes. Variants with a minor allele frequency of <0.05% were assessed for pathogenicity by using existing mutation databases and in silico predictive algorithms.
In 1 of 33 patients, a likely pathogenic mutation was detected. The added yield of genetic testing with NGS of 179 additional genes is 3% in patients with IVF. In 15% of patients, 1 or multiple variants of uncertain clinical significance were detected.
The added yield of genetic screening of extended NGS panels in patients initially diagnosed with IVF is minimal. Routine analysis of large diagnostic NGS panels is therefore not recommended.
特发性室颤（IVF）是一种罕见的原发性心脏心律失常综合征，在经过全面临床评估后仍无法确定潜在病因的情况下，在复苏性心脏骤停的受害者中被诊断出来，其特征是有记录的室颤。在一些患者中，可以检测到导致疾病的基因突变，这有助于对患者进行治疗和随访。随着其更广泛的应用和成本的降低，下一代测序（NGS）的可行性有所提高。
本研究旨在评估 NGS 在 IVF 患者中的诊断效果。
共纳入 33 例最初被诊断为 IVF 的患者（平均年龄 53 ± 15 岁；14 例（42%）为男性）。在所有纳入的患者中，对 33 个基因和 DPP6 单倍型进行 NGS 检测，未发现致病性突变。基因筛查包括对 179 个附加基因的 NGS 检测。对等位基因频率<0.05%的变异进行致病性评估，方法是使用现有的突变数据库和计算机预测算法。
在 33 例患者中的 1 例中发现了一种可能的致病性突变。对 IVF 患者进行 NGS 检测 179 个附加基因的额外检测的阳性率为 3%。在 15%的患者中，检测到 1 个或多个临床意义不确定的变异。
对最初诊断为 IVF 的患者进行扩展 NGS 面板的基因筛查的附加收益很小。因此，不建议常规分析大型诊断 NGS 面板。
