Martínez-Barrios Estefanía, Greco Andrea, Cesar Sergi, Díez-López Carles, Cruzalegui José, Díez-Escuté Nuria, Cerralbo Patricia, Chipa Fredy, Zschaeck Irene, Grassi Simone, Oliva Antonio, Balderrábano Norma, Toro Rocío, Sarquella-Brugada Georgia, Campuzano Oscar
Pediatric Arrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, 08950 Esplugues de Llobregat, Spain.
Pediatric Arrhythmias, Genetic Cardiology and Sudden Death, Cardiovascular Diseases in the Development, Institut de Recerca Sant Joan de Déu, 08950 Esplugues de Llobregat, Spain.
iScience. 2025 Mar 27;28(5):112300. doi: 10.1016/j.isci.2025.112300. eCollection 2025 May 16.
Genetic analysis identified the cause of the disease in inherited arrhythmogenic syndromes. A clinically actionable genetic diagnosis requires an accurate interpretation following the current guidelines. Practically half of the genetic diagnoses remain inconclusive due to the identification of variants of uncertain significance. An update can help shed light on uncertain results. No specific time frame has been set for updating an ambiguous diagnosis. We carried out an analysis of the available reclassification/reinterpretation data concerning genetic diagnosis in inherited arrhythmogenic syndromes. We aim to determine an appropriate interval for updating a conclusive classification. Genetic diagnoses achieved without following current guidelines should be updated immediately. An ambiguous result obtained following the current guidelines should be updated no more than 5 years after the first analysis. There are still questions to be resolved regarding the legal responsibility or who should assume the economic cost of updating a genetic diagnosis.
基因分析确定了遗传性心律失常综合征的病因。临床可操作的基因诊断需要按照现行指南进行准确解读。实际上，由于发现了意义未明的变异，几乎一半的基因诊断结果仍不明确。更新可以帮助阐明不确定的结果。对于更新不明确的诊断，尚未设定具体的时间框架。我们对遗传性心律失常综合征基因诊断的现有重新分类/重新解读数据进行了分析。我们旨在确定更新确定性分类的合适间隔。未遵循现行指南得出的基因诊断结果应立即更新。遵循现行指南获得的不明确结果应在首次分析后不超过5年进行更新。关于更新基因诊断的法律责任或应由谁承担经济成本，仍有一些问题有待解决。
