Ramond F, Janin A, Di Filippo S, Chanavat V, Chalabreysse L, Roux-Buisson N, Sanlaville D, Touraine R, Millat G
Genetics Department, CHU-Hôpital Nord, Saint-Etienne, France.
Laboratoire de Cardiogénétique Moléculaire, Hospices Civils de Lyon, Lyon, France.
Clin Genet. 2017 Jan;91(1):126-130. doi: 10.1111/cge.12780. Epub 2016 Apr 26.
Left ventricular noncompaction cardiomyopathy (LVNC) is a clinically heterogeneous disorder characterized by a trabecular meshwork and deep intertrabecular myocardial recesses that communicate with the left ventricular cavity. Several genetic causes of LVNC have been reported, with variable modes of inheritance, including autosomal dominant and X-linked inheritance, but relatively few responsible genes have been identified. A NGS workflow, based on a panel of 95 genes developed for sequencing most prevalent sudden cardiac death-causing genes, was used to make a rapid and costless molecular diagnosis in two siblings with a severe noncompaction cardiomyopathy starting prenatally and leading to rapid cardiac failure. For the first time, a total homozygous PKP2 deletion was identified. This molecular defect was further confirmed by MLPA and array-comparative genomic hybridization (CGH). Heterozygous PKP2 mutations are usually reported in a significant proportion of Arrhythmogenic Right Ventricular Cardiomyopathy cases. Our results show, for the first time, the involvement of PKP2 in severe cardiomyopathy with ventricular non compaction.
左心室致密化不全心肌病（LVNC）是一种临床异质性疾病，其特征为小梁网状结构以及与左心室腔相通的小梁间心肌深陷。已有多种LVNC的遗传病因被报道，遗传方式多样，包括常染色体显性遗传和X连锁遗传，但已确定的致病基因相对较少。我们使用了一种基于95个基因的二代测序（NGS）流程，该流程是为对最常见的致心性猝死基因进行测序而开发的，用于对两名患有严重致密化不全心肌病的同胞进行快速且低成本的分子诊断，这两名患者从产前起病，最终迅速发展为心力衰竭。首次鉴定出PKP2基因完全纯合缺失。该分子缺陷通过多重连接探针扩增（MLPA）和阵列比较基因组杂交（CGH）进一步得到证实。在相当一部分致心律失常性右心室心肌病病例中通常会报道杂合性PKP2突变。我们的结果首次表明PKP2参与了伴有心室致密化不全的严重心肌病。
