Mitochondrial encephalopathy is a neurological disorder caused by impaired mitochondrial function and energy production. One of the genetic causes of this condition is the mutation of MT-TN, a gene that encodes the mitochondrial transfer RNA (tRNA) for asparagine. MT-TN mutations affect the stability and structure of the tRNA, resulting in reduced protein synthesis and complex enzymatic deficiency of the mitochondrial respiratory chain. Our patient cohort manifests with epileptic encephalopathy, ataxia, hypotonia, and bilateral basal ganglia calcification, which differs from previously reported cases. MT-TN mutation deficiency leads to decreased basal and maximal oxygen consumption rates, disrupted spare respiratory capacity, declined mitochondrial membrane potential, and impaired ATP production. Moreover, MT-TN mutations promote mitophagy, a process of selective degradation of damaged mitochondria by autophagy. Excessive mitophagy further leads to mitochondrial biogensis as a compensatory mechanism. In this study, we provided evidence of pathogenicity for two MT-TN mutations, m.5688 T > C and m.G5691A, explored the molecular mechanisms, and summarized the clinical manifestations of MT-TN mutations. Our study expanded the genotype and phenotypic spectrum and provided new insight into mt-tRNA (Asn)-associated mitochondrial encephalopathy.

中文翻译：

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MT-TN 突变导致进行性线粒体脑病并促进线粒体自噬

线粒体脑病是一种由线粒体功能和能量产生受损引起的神经系统疾病。这种情况的遗传原因之一是 MT-TN 突变，该基因编码天冬酰胺线粒体转移 RNA (tRNA)。MT-TN 突变影响 tRNA 的稳定性和结构，导致蛋白质合成减少和线粒体呼吸链复杂的酶缺乏。我们的患者队列表现为癫痫性脑病、共济失调、肌张力减退和双侧基底节钙化，这与之前报道的病例不同。MT-TN 突变缺陷导致基础耗氧率和最大耗氧率降低、备用呼吸能力受损、线粒体膜电位下降以及 ATP 产生受损。此外，MT-TN突变促进线粒体自噬，这是一种通过自噬选择性降解受损线粒体的过程。过度的线粒体自噬进一步导致线粒体生物发生作为一种补偿机制。在本研究中，我们提供了两种MT-TN突变m.5688 T > C和m.G5691A的致病性证据，探讨了分子机制，并总结了MT-TN突变的临床表现。我们的研究扩大了基因型和表型谱，并为 mt-tRNA (Asn) 相关线粒体脑病提供了新的见解。