2例罕见的DSC2隐性遗传性致心律失常性心肌病患者的临床表型及基因型分析

The phenotype and genotype analysis of two rare cases of arrhythmogenic cardiomyopathy with DSC2 autosomal recessive inheritance

致心律失常性心肌病(ACM)是一种以心肌细胞凋亡且被纤维或脂肪替代为主要特征的心肌病,多累及右心室(即致心律失常性右心室心肌病,ARVC),也可以累及左心室或双心室,主要表现为常染色体显性遗传,也存在罕见的常染色体隐性遗传方式。目前国内尚无DSC2隐性遗传性ACM的相关报道。本文报道了2例罕见的年轻中国汉族DSC2隐性遗传性ACM先证者,均进行了心脏移植术。先证者1为16岁男性,确诊为双心室型ACM,心力衰竭,携带此前无报道的DSC2 c.2219C>A(p.Ser740Ter)纯合变异,父母为杂合型;先证者2为33岁男性,确诊为ARVC,携带非母源的DSC2 c.1818del(p.Phe608LeufsTer18)和母源的c.527C>T(p.Phe176Leu)杂合变异,构成复合杂合的可能性大。两名先证者的非近亲、无相关家族史的父母均无相关临床表现。此结果丰富了国内和国际的基因型谱和临床表型谱,同时提示在早发且严重表型的ACM/ARVC患者中应考虑隐性遗传的罕见可能,而生物学父母样本和详尽的临床检查及随访结果对于遗传模式的判断也至关重要。

Arrhythmogenic cardiomyopathy(ACM)is a type of cardiomyopathy characterized by myocardial apoptosis and fatty or fibrofatty replacement of right(i.e.arrhythmogenic right ventricular cardiomyopathy,ARVC)ventricle and/or left ventricle.It is usually inherited as an autosomal dominant pattern,and rare autosomal recessive cases are also reported.At present,there are no reports of DSC2 associated recessive ACM in China.Here,two rare young Chinese patients with desmocollin-2(DSC2)recessive ACM who underwent heart transplantation surgery are reported.Proband 1,male,diagnosed with biventricular ACM and heart failure at the age of 16,carries a novel DSC2 homozygous variant of c.2219C>A(p.Ser740Ter)inherited from heterozygous parents.Proband 2,male,diagnosed with ARVC at the age of 33,carries potential compound heterozygous DSC2 variants of non-maternal c.1818del(p.Phe608LeufsTer18)and maternal c.527C>T(p.Phe176Leu).The nonconsanguineous parents of both probands without relevant family history have no relevant clinical manifestations.These results enrich the genotype and phenotype profiles both domestically and internationally,and suggest that the rare possibility of recessive inheritance should be considered in ACM/ARVC patients with early-onset and severe phenotypes.Biological parental samples with detailed clinical examination and follow-up results are also crucial for determining inheritance patterns.