Marey Isabelle, Fressart Véronique, Rambaud Caroline, Fornes Paul, Martin Laurent, Grotto Sarah, Alembik Yves, Gorka Hervé, Millat Gilles, Gandjbakhch Estelle, Bordet Céline, de la Grandmaison Geoffroy Lorin, Richard Pascale, Charron Philippe
APHP, Reference Center for Hereditary Heart Diseases, Department of Genetics, Pitié-Salpêtrière Hospital, 75013 Paris, France.
APHP, Cardiogenetics and Myogenetics Unit, Metabolic Biochemistry Department, Pitié-Salpêtrière Hospital Group, 75013 Paris, France.
Open Med (Wars). 2020 May 19;15(1):435-446. doi: 10.1515/med-2020-0150. eCollection 2020.
Post-mortem genetic analyses may help to elucidate the cause of cardiac death. The added value is however unclear when a cardiac disease is already suspected or affirmed. Our aim was to study the feasibility and medical impact of post-mortem genetic analyses in suspected cardiomyopathy. We studied 35 patients with cardiac death and suspected cardiomyopathy based on autopsy or clinical data. After targeted sequencing, we identified 15 causal variants in 15 patients (yield 43%) in sarcomeric ( = 8), desmosomal ( = 3), lamin A/C ( = 3) and transthyretin ( = 1) genes. The results had various impacts on families, i.e. allowed predictive genetic testing in relatives (15 families), planned early therapeutics based on the specific underlying gene (5 families), rectified the suspected cardiomyopathy subtype (2 families), assessed the genetic origin of cardiomyopathy that usually has an acquired cause (1 family), assessed the diagnosis in a patient with uncertain borderline cardiomyopathy (1 family), reassured the siblings because of a mutation (2 families) and allowed prenatal testing (1 family). Our findings suggest that post-mortem molecular testing should be included in the strategy of family care after cardiac death and suspected cardiomyopathy, since genetic findings provide additional information useful for relatives, which are beyond conventional autopsy.
尸检基因分析可能有助于阐明心源性死亡的原因。然而，当已经怀疑或确诊患有心脏病时，其附加价值尚不清楚。我们的目的是研究尸检基因分析在疑似心肌病中的可行性和医学影响。我们基于尸检或临床数据研究了35例心源性死亡且疑似心肌病的患者。经过靶向测序，我们在15例患者（检出率43%）中鉴定出15个致病变异，分别位于肌节蛋白（=8）、桥粒蛋白（=3）、核纤层蛋白A/C（=3）和转甲状腺素蛋白（=1）基因中。这些结果对家庭产生了各种影响，即允许对亲属进行预测性基因检测（15个家庭）、基于特定潜在基因规划早期治疗（5个家庭）、纠正疑似心肌病亚型（2个家庭）、评估通常由后天因素引起的心肌病的遗传起源（1个家庭）、评估一名边缘性心肌病诊断不明确患者的诊断（1个家庭）、因一个突变让兄弟姐妹放心（2个家庭）以及允许进行产前检测（1个家庭）。我们的研究结果表明，尸检分子检测应纳入心源性死亡和疑似心肌病后的家庭护理策略中，因为基因检测结果可为亲属提供超出传统尸检的额外有用信息。
