Pandolfo M
Département de Médecine, Université de Montréal Adjunct Professor, Québec, Canada.
Neuromuscul Disord. 1998 Aug;8(6):409-15. doi: 10.1016/s0960-8966(98)00039-x.
Friedreich ataxia, the most frequent cause of inherited ataxia, is due in most cases to a large expansion of an intronic GAA repeat, resulting in decreased expression of the target frataxin gene. The autosomal recessive inheritance of the disease gives this triplet repeat mutation some unique features of natural history and evolution. Frataxin is a mitochondrial protein that has homologues in yeast and even in gram negative bacteria. Yeast deficient in the frataxin homologue accumulate iron in mitochondria and show increased sensitivity to oxidative stress. This suggests that Friedreich ataxia is caused by mitochondrial dysfunction and free radical toxicity.
弗里德赖希共济失调是遗传性共济失调最常见的病因，在大多数情况下，是由于内含子GAA重复序列的大量扩增，导致目标铁调素基因的表达降低。该疾病的常染色体隐性遗传使这种三联体重复突变具有一些独特的自然病史和演变特征。铁调素是一种线粒体蛋白，在酵母甚至革兰氏阴性细菌中都有同源物。缺乏铁调素同源物的酵母会在线粒体中积累铁，并对氧化应激表现出更高的敏感性。这表明弗里德赖希共济失调是由线粒体功能障碍和自由基毒性引起的。
