Abstract：
Arrhythmogenic cardiomyopathy (AC) is a rare, heritable myocardial disorder that is a leading cause of ventricular arrhythmia and sudden cardiac death (SCD) in young people. Desmoplakin (DSP) mutations account for 3-20% of AC cases. However, the number of patients with DSP mutations is extremely small in all published reports and genotype-phenotype correlations are scant and mostly non-gene-specific.
A 45-year-old man was admitted after an out-of-hospital cardiac arrest, with documented ventricular fibrillation. He had no previous history of heart disease or family history of SCD or cardiomyopathy. The cardiac magnetic resonance showed a mildly dilated left ventricle with an ejection fraction of 30% and a non-dilated right ventricle with mildly depressed systolic function, and extensive subepicardial late gadolinium enhancement. Genetic screening identified a heterozygote nonsense mutation in DSP (NM_004415.2: c.478 C > T; p.Arg160Ter). Cascade genetic screening of the relatives revealed a high prevalence of the genotype and cutaneous phenotype, but a very low penetrance of the cardiac phenotype.
We report a case of SCD and an autosomal dominant mutation in DSP that causes arrhythmogenic dilated cardiomyopathy/AC. Like the recessive mutation in DSP known to cause Carvajal syndrome, Arg160Ter may be associated with cutaneous abnormalities.
A 45-year-old man was admitted after an out-of-hospital cardiac arrest, with documented ventricular fibrillation. He had no previous history of heart disease or family history of SCD or cardiomyopathy. The cardiac magnetic resonance showed a mildly dilated left ventricle with an ejection fraction of 30% and a non-dilated right ventricle with mildly depressed systolic function, and extensive subepicardial late gadolinium enhancement. Genetic screening identified a heterozygote nonsense mutation in DSP (NM_004415.2: c.478 C > T; p.Arg160Ter). Cascade genetic screening of the relatives revealed a high prevalence of the genotype and cutaneous phenotype, but a very low penetrance of the cardiac phenotype.
We report a case of SCD and an autosomal dominant mutation in DSP that causes arrhythmogenic dilated cardiomyopathy/AC. Like the recessive mutation in DSP known to cause Carvajal syndrome, Arg160Ter may be associated with cutaneous abnormalities.
摘要：
心律失常性心肌病（AC）是一种罕见的，遗传性心肌病，是年轻人室性心律失常和心源性猝死（SCD）的主要原因。Desmoplakin（DSP）突变占AC病例的3-20％。然而,在所有已发表的报告中,有DSP突变的患者数量非常少,而且基因型-表型相关性很少,而且大多是非基因特异性的.
一名45岁的男子在院外心脏骤停后入院，有记录的心室纤颤。他以前没有心脏病史或SCD或心肌病的家族史。心脏磁共振显示左心室轻度扩张，射血分数为30％，右心室未扩张，收缩功能轻度下降，和广泛的心外膜下晚钆增强。遗传筛选鉴定了DSP中的杂合子无义突变(NM_004415.2:c.478C>T;p.Arg160Ter)。亲属的级联遗传筛查显示基因型和皮肤表型的患病率很高，但是心脏表型的外显率非常低。
我们报告了一例SCD和DSP中的常染色体显性突变导致心律失常性扩张型心肌病/AC。就像已知会导致卡瓦哈尔综合征的DSP中的隐性突变一样，Arg160Ter可能与皮肤异常有关。
一名45岁的男子在院外心脏骤停后入院，有记录的心室纤颤。他以前没有心脏病史或SCD或心肌病的家族史。心脏磁共振显示左心室轻度扩张，射血分数为30％，右心室未扩张，收缩功能轻度下降，和广泛的心外膜下晚钆增强。遗传筛选鉴定了DSP中的杂合子无义突变(NM_004415.2:c.478C>T;p.Arg160Ter)。亲属的级联遗传筛查显示基因型和皮肤表型的患病率很高，但是心脏表型的外显率非常低。
我们报告了一例SCD和DSP中的常染色体显性突变导致心律失常性扩张型心肌病/AC。就像已知会导致卡瓦哈尔综合征的DSP中的隐性突变一样，Arg160Ter可能与皮肤异常有关。
