1. Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.
Cell J. 2012 Summer;14(2):98-101. Epub 2012 Aug 31.
Autism results from developmental factors that affect many or all functional brain systems. Brain is one of tissues which are crucially in need of adenosine triphosphate (ATP). Autism is noticeably affected by mitochondrial dysfunction which impairs energy metabolism. Considering mutations within ATPase 6, ATPase 8 and tRNA(Lys) genes, associated with different neural diseases, and the main role of ATPase 6/8 in energy generation, we decided to investigate mutations on these mtDNA-encoded genes to reveal their roles in autism pathogenesis.
In this experimental study, mutation analysis for the mentioned genes were performed in a cohort of 24 unrelated patients with idiopathic autism by employing amplicon sequencing of mtDNA fragments.
In this study, 12 patients (50%) showed point mutations that represent a significant correlation between autism and mtDNA variations. Most of the identified substitutions (55.55%) were observed on MT-ATP6, altering some conserved amino acids to other ones which could potentially affect ATPase 6 function. Mutations causing amino acid replacement denote involvement of mtDNA genes, especially ATPase 6 in autism pathogenesis.
MtDNA mutations in relation with autism could be remarkable to realize an understandable mechanism of pathogenesis in order to achieve therapeutic solutions.
自闭症是由影响许多或所有大脑功能系统的发育因素引起的。大脑是急需三磷酸腺苷（ATP）的组织之一。自闭症明显受到损害能量代谢的线粒体功能障碍的影响。鉴于与不同神经疾病相关的 ATPase 6、ATPase 8 和 tRNA（Lys）基因内的突变，以及 ATPase 6/8 在能量产生中的主要作用，我们决定研究这些线粒体 DNA 编码基因的突变，以揭示它们在自闭症发病机制中的作用。
在这项实验研究中，通过扩增子测序 mtDNA 片段，对 24 名无关的特发性自闭症患者进行了上述基因的突变分析。
在这项研究中，有 12 名患者（50%）表现出点突变，这表明自闭症与 mtDNA 变异之间存在显著相关性。大多数鉴定出的取代（55.55%）发生在 MT-ATP6 上，将一些保守的氨基酸改变为其他可能影响 ATPase 6 功能的氨基酸。导致氨基酸替换的突变表明 mtDNA 基因，特别是 ATPase 6 参与了自闭症的发病机制。
与自闭症相关的 mtDNA 突变可能有助于实现对发病机制的理解机制，以实现治疗解决方案。
