Do mitochondria contribute to left ventricular non-compaction cardiomyopathy? New findings from myocardium of patients with left ventricular non-compaction cardiomyopathy
Do mitochondria contribute to left ventricular non-compaction cardiomyopathy? New findings from myocardium of patients with left ventricular non-compaction cardiomyopathy
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线粒体会导致左心室致密化不全心肌病吗？
DOI：
10.1016/j.ymgme.2013.02.004
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发表时间：
2013-05-01
影响因子：
3.8
通讯作者：
Wei, Yingjie
中科院分区：
文献类型：
--
作者：
Liu, Shenghua;Bai, Yuanyuan;Wei, Yingjie
背景资料：左心室致密化不全型心肌病（LVNC）是一种罕见的先天性心肌病，与线粒体突变有关！但对LVNC患者心肌线粒体DNA的研究尚未见报道。为了确定新的候选mtDNA变异，可能是负责LVNC的发病机制，心肌标本进行了检查，调查致病mtDNA variants.Materials和方法：样品从6例患者被诊断为LVNC和接受心脏移植进行了分析。结果：心肌线粒体DNA序列分析共发现227个替换变异，其中编码变异157个，非编码变异70个。来自一名LVNC患者的MT-CO 3中的m.9856T>C（Ile 217 Thr）突变被发现是非单倍型群相关的变体，并且在mtDB人类线粒体基因组数据库中是罕见的，这表明该变体可能是致病性的。LVNC组与正常对照组比较，线粒体DNA拷贝数差异有统计学意义。电镜下左心室心肌线粒体形态异常，肌节结构紊乱。结论：心肌线粒体DNA序列变异的鉴定有助于进一步研究心肌线粒体DNA突变在LVNC发病中的作用。线粒体DNA拷贝数测定显示LVNC患者心肌线粒体DNA含量低于正常对照组（P
Background: Left ventricular non-compaction cardiomyopatliy (LVNC) is a rare congenital cardiomyopathy that is associated with mutations in mitochondria! DNA (mtDNA), however, no study of myocardium mtDNA of LVNC patients has been reported. To identify novel candidate mtDNA variants that may be responsible for the pathogenesis of LVNC, myocardial specimens were examined to investigate pathogenic mtDNA variants.Materials and methods: Samples from six patients who were diagnosed with LVNC and underwent heart transplantation were analyzed. The sequence and copy number of mtDNA from these samples were determined by Sanger sequencing and fluorescence-based quantitative polymerase chain reaction, respectively.Results: Myocardial mtDNA sequences analysis revealed 227 substitution variants, including 157 coding variants and 70 non-coding variants. An m.9856T>C (Ile217Thr) mutation in MT-CO3 from one LVNC patient was found to be a non-haplogroup associated variant, and was rare in the mtDB Human Mitochondrial Genome Database, suggesting that the variant may be pathogenic. And there was statistically significant difference in mtDNA copy number between LVNC patients and normal control subjects. Electron microscopy (EM) of left ventricular myocardium showed abnormality in mitochondria( morphology and disordered sarcomeric organization.Conclusion: The identification of mtDNA sequence variants in myocardial specimens may be helpful for further investigation of the underlying pathogenic implications of myocardial mtDNA mutations in LVNC. However, measurement of mtDNA copy number showed that there was lower mtDNA content in myocardium of LVNC patients than in normal controls (P