Homozygous PKP2 deletion associated with neonatal left ventricle noncompaction
Homozygous PKP2 deletion associated with neonatal left ventricle noncompaction
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DOI：
10.1111/cge.12780
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发表时间：
2017-01-01
影响因子：
3.5
通讯作者：
Millat, G.
中科院分区：
文献类型：
--
作者：
Ramond, F.;Janin, A.;Millat, G.
左心室致密化不全性心肌病（LVNC）是一种临床异质性疾病，其特征是小梁网和与左心室腔相通的深层小梁间心肌凹陷。LVNC的几种遗传原因已被报道，具有可变的遗传模式，包括常染色体显性遗传和X连锁遗传，但相对较少的责任基因已被确定。NGS工作流程基于一组95个基因，用于测序最常见的心脏性猝死基因，用于对两个兄弟姐妹进行快速和无成本的分子诊断，他们患有严重的致密化不全心肌病，从产前开始并导致快速心力衰竭。这是第一次发现完全纯合的PKP2缺失。MLPA和阵列比较基因组杂交（CGH）进一步证实了这一分子缺陷。杂合子PKP2突变通常在致心律失常性右室心肌病病例中报告。我们的研究结果表明，第一次，PKP2参与严重心肌病心室致密化不全。
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.