Friedreich's ataxia.
Friedreich's ataxia, the most common hereditary ataxia, is caused by expansion of a GAA triplet located within the first intron of the frataxin gene on chromosome 9q13. There is a clear correlation between size of the expanded repeat and severity of the phenotype. Frataxin is a mitochondrial protein that plays a role in iron homeostasis. Deficiency of frataxin results in mitochondrial iron accumulation, defects in specific mitochondrial enzymes, enhanced sensitivity to oxidative stress, and eventually free-radical mediated cell death. Friedreich's ataxia is considered a nuclear encoded mitochondrial disease. This review discusses the major and rapid progress made in Friedreich's ataxia from gene mapping and identification of the gene to pathogenesis and encouraging therapeutic implications.
Alper
Gulay
G
Division of Child Neurology, Department of Pediatrics, Children's Hospital of Pittsburgh, 3705 Fifth Avenue, Pittsburgh, PA 15213, USA.
Narayanan
Vinodh
V
D005621:Friedreich Ataxia / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy; D006801:Humans; D033862:Iron-Binding Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D017354:Point Mutation / Q000502:physiology; D019680:Trinucleotide Repeat Expansion / Q000502:physiology; D000096923:Frataxin
D033862:Iron-Binding Proteins; D000096923:Frataxin