Abstract：
The diagnosis of cardiomyopathy often relies on the subjective judgment of pathologists due to the variety of morphologic changes in the condition and its low specificity. This uncertainty can contribute to unexplained sudden cardiac deaths (USCD). To enhance the accuracy of hereditary cardiomyopathy diagnosis in forensic medicine, we proposed a combination of molecular autopsy and pathologic autopsy. By analyzing 16 deceased patients suspected of cardiomyopathy, using whole exome sequencing (WES) in molecular autopsy, and applying a combined diagnostic strategy, the study found pathogenic or likely pathogenic variants in 6 cases. Out of the 16 cases, cardiomyopathy was confirmed in 3, while 3 exhibited conditions consistent with it. Data for 4 cases was inconclusive, and cardiomyopathy was ruled out in 6. Notably, a novel variant of the TTN gene was identified. This research suggests that a grading diagnostic strategy, combining molecular and pathological evidence, can improve the accuracy of forensic cardiomyopathy diagnosis. This approach provides a practical model and strategy for precise forensic cause-of-death determination, addressing the limitations of relying solely on morphologic assessments in cardiomyopathy cases, and integrating genetic information for a more comprehensive diagnosis.
摘要：
心肌病的诊断通常依赖于病理学家的主观判断，由于病情的形态学变化和特异性低。这种不确定性可能导致无法解释的心脏猝死（USCD）。提高遗传性心肌病法医学诊断的准确性,我们提出了分子尸检和病理尸检的结合。通过分析16名疑似心肌病的死亡患者，在分子尸检中使用全外显子组测序（WES），并应用联合诊断策略，该研究发现6例患者有致病性或可能的致病性变异。在16个案例中，在3例中证实了心肌病，而3例表现出与之一致的条件。4例数据无定论,心肌病在6年被排除。值得注意的是,鉴定了TTN基因的新变体。这项研究表明，分级诊断策略，结合分子和病理证据，可以提高法医心肌病诊断的准确性。这种方法为精确的法医死因判定提供了一个实用的模型和策略,解决在心肌病病例中仅仅依赖形态学评估的局限性，整合遗传信息以进行更全面的诊断。
