Nogueira Célia, Carrozzo Rosalba, Vilarinho Laura, Santorelli Filippo M
Department of Genetics, Centro de Genética Médica Jacinto de Magalhães/INSA, Porto, Portugal.
J Child Neurol. 2011 Jul;26(7):866-75. doi: 10.1177/0883073811402072. Epub 2011 May 13.
Most inherited mitochondrial diseases in infants result from mutations in nuclear genes encoding proteins with specific functions targeted to the mitochondria rather than primary mutations in the mitochondrial DNA (mtDNA) itself. In the past decade, a growing number of syndromes associated with dysfunction resulting from tissue-specific depletion of mtDNA have been reported in infants. MtDNA depletion syndrome is transmitted as an autosomal recessive trait and causes respiratory chain dysfunction with prominent neurological, muscular, and hepatic involvement. Mendelian diseases characterized by defective mitochondrial protein synthesis and combined respiratory chain defects have also been described in infants and are associated with mutations in nuclear genes that encode components of the translational machinery. In the present work, we reviewed current knowledge of clinical phenotypes, their relative frequency, spectrum of mutations, and possible pathogenic mechanisms responsible for infantile disorders of oxidative metabolism involved in correct mtDNA maintenance and protein production.
大多数婴儿遗传性线粒体疾病是由核基因中的突变引起的，这些核基因编码具有特定功能的蛋白质，这些蛋白质靶向线粒体，而不是线粒体DNA（mtDNA）本身的原发性突变。在过去十年中，越来越多与婴儿mtDNA组织特异性耗竭导致的功能障碍相关的综合征被报道。mtDNA耗竭综合征以常染色体隐性性状遗传，导致呼吸链功能障碍，并伴有明显的神经、肌肉和肝脏受累。以线粒体蛋白质合成缺陷和联合呼吸链缺陷为特征的孟德尔疾病也在婴儿中被描述，并且与编码翻译机制成分的核基因中的突变有关。在本研究中，我们回顾了当前关于临床表型、它们的相对频率、突变谱以及负责正确mtDNA维持和蛋白质产生的婴儿氧化代谢障碍的可能致病机制的知识。
