BACKGROUND Dilated cardiomyopathy (DCM) is a condition characterized by dilatation and systolic dysfunction of the left ventricle in the absence of severe coronary artery disease or abnormal loading conditions. Mutations in the titin (TTN) and lamin A/C (LMNA) genes are the two most significant contributors in familial DCM. Previously mutations in the desmoplakin (DSP) gene have been associated with arrhythmogenic right ventricular cardiomyopathy (ARVC) and more recently with DCM. METHODS We describe the cardiac phenotype related to a DSP mutation which was identified in ten unrelated Finnish index patients using next-generation sequencing. Sanger sequencing was used to verify the presence of this DSP variant in the probands' relatives. Medical records were obtained, and clinical evaluation was performed. RESULTS We identified DSP c.6310delA, p.(Thr2104Glnfs*12) variant in 17 individuals of which 11 (65%) fulfilled the DCM diagnostic criteria. This pathogenic variant presented with left ventricular dilatation, dysfunction and major ventricular arrhythmias. Two patients showed late gadolinium enhancement (LGE) and myocardial edema on cardiac magnetic resonance imaging (MRI) that may suggest inflammatory process at myocardium. CONCLUSIONS The patients diagnosed with DCM showed an arrhythmogenic phenotype as well as SCD at young age supporting the recently proposed concept of arrhythmogenic cardiomyopathy. This study also demonstrates relatively low penetrance of truncating DSP variant in the probands' family members by the age of 40. Further studies are needed to elucidate the possible relations between myocardial inflammation and pathogenic DSP variants.

中文翻译：

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DSP p.(Thr2104Glnfs*12) 变异体不同程度地表现为早发性严重心律失常和左心室心肌病。

背景技术扩张型心肌病(DCM)是一种在没有严重冠状动脉疾病或异常负荷情况下以左心室扩张和收缩功能障碍为特征的病症。肌联蛋白 (TTN) 和核纤层蛋白 A/C (LMNA) 基因突变是家族性 DCM 的两个最重要的影响因素。此前，桥粒斑蛋白 (DSP) 基因突变与致心律失常性右心室心肌病 (ARVC) 相关，最近又与 DCM 相关。方法 我们描述了与 DSP 突变相关的心脏表型，该突变是使用下一代测序在 10 名不相关的芬兰指数患者中发现的。桑格测序用于验证先证者亲属中是否存在这种 DSP 变体。获取医疗记录并进行临床评估。结果 我们在 17 名个体中发现了 DSP c.6310delA, p.(Thr2104Glnfs*12) 变异，其中 11 名 (65%) 符合 DCM 诊断标准。这种致病变异表现为左心室扩张、功能障碍和严重室性心律失常。两名患者在心脏磁共振成像 (MRI) 上显示晚期钆增强 (LGE) 和心肌水肿，这可能表明心肌存在炎症过程。结论 诊断为 DCM 的患者在年轻时表现出致心律失常表型以及 SCD，支持最近提出的致心律失常心肌病的概念。这项研究还表明，先证者家庭成员在 40 岁时截短 DSP 变异的外显率相对较低。需要进一步研究来阐明心肌炎症与致病性 DSP 变异之间的可能关系。