Complete loss of expression of the ANT1 gene causing cardiomyopathy and myopathy
Complete loss of expression of the ANT1 gene causing cardiomyopathy and myopathy
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DOI：
10.1136/jmedgenet-2011-100504
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发表时间：
2012-02-01
影响因子：
4
通讯作者：
de Camaret, Benedicte Mousson
中科院分区：
文献类型：
--
作者：
Echaniz-Laguna, Andoni;Chassagne, Maite;de Camaret, Benedicte Mousson
研究了一名以先天性白内障、肥厚性心肌病、肌病和乳酸性酸中毒为特征的常染色体隐性线粒体疾病患者的ANT1基因，该基因编码ADP/ATP转座酶1。方法和结果ANT1测序结果显示，该患者为新的核苷酸变异c.111+1G -> a纯合子，消除了内含子1的不变GT剪接供体位点。ANT1转录本在肌肉和皮肤成纤维细胞中均未检测到。发现代谢谱明显异常，骨骼肌显示异常线粒体的急剧增殖，线粒体质量增加，线粒体DNA缺失。未观察到编码人类普遍存在的ADP/ATP转位酶亚型的ANT3基因转录水平的补偿性增加。患者杂合子母亲临床、生化、病理特征正常。结论ANT1基因表达完全缺失导致以心肌病和肌病为主要特征的临床综合征。本报告扩展了ant1相关人类疾病的临床谱，并强调了线粒体ADP/ATP载体在肌肉功能和人类肌病病理生理中的关键作用。
Background The ANT1 gene, encoding ADP/ATP translocase 1, was investigated in an adult patient with an autosomal recessive mitochondrial disorder characterised by congenital cataracts, hypertrophic cardiomyopathy, myopathy and lactic acidosis.Methods and results ANT1 sequencing showed that the patient was homozygous for a new nucleotide variation, c.111+1G -> A, abolishing the invariant GT splice donor site of intron 1. The ANT1 transcript was undetectable in both muscle and skin fibroblasts. A markedly abnormal metabolic profile was found, and skeletal muscle showed a dramatic proliferation of abnormal mitochondria, increased mitochondrial mass, and multiple mitochondrial DNA deletions. No compensating increase in the transcript level of the ANT3 gene, which encodes the human ubiquitous isoform of the ADP/ATP translocase, was observed. The patient's heterozygous mother had normal clinical, biochemical and pathological features.Conclusions Complete loss of expression of the ANT1 gene causes a clinical syndrome mainly characterised by cardiomyopathy and myopathy. This report expands the clinical spectrum of ANT1-related human diseases, and emphasises the crucial role of the mitochondrial ADP/ATP carriers in muscle function and pathophysiology of human myopathies.