Friedreich Ataxia: From GAA Triplet–Repeat Expansion to Frataxin Deficiency

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Detection of interruptions in the GAA trinucleotide repeat expansion in the FXN gene of Friedreich ataxia.

Friedreich ataxia is a neurodegenerative disorder caused by the expansion of a GAA trinucleotide repeat sequence within the first intron of the FXN gene. Interruptions in the GAA repeat may serve to alleviate the inhibitory effects of the GAA expansion on FXN gene expression and to decrease pathogenicity. We have developed a simple and rapid PCR- and restriction enzyme-based assay to assess the...

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Frataxin levels in peripheral tissue in Friedreich ataxia

OBJECTIVE Friedreich ataxia (FRDA) is an autosomal recessive ataxia resulting from mutations in the frataxin gene (FXN). Such mutations, usually expanded guanine-adenine-adenine (GAA) repeats, give rise to decreased levels of frataxin protein in both affected and unaffected tissues. The goal was to understand the relationship of frataxin levels in peripheral tissues to disease status. METHODS...

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Long intronic GAA repeats causing Friedreich ataxia impede transcription elongation

Friedreich ataxia is a degenerative disease caused by deficiency of the protein frataxin (FXN). An intronic expansion of GAA triplets in the FXN-encoding gene, FXN, causes gene silencing and thus reduced FXN protein levels. Although it is widely assumed that GAA repeats block transcription via the assembly of an inaccessible chromatin structure marked by methylated H3K9, direct proof for this i...

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HDAC Inhibitors Correct Frataxin Deficiency in a Friedreich Ataxia Mouse Model

BACKGROUND Friedreich ataxia, an autosomal recessive neurodegenerative and cardiac disease, is caused by abnormally low levels of frataxin, an essential mitochondrial protein. All Friedreich ataxia patients carry a GAATTC repeat expansion in the first intron of the frataxin gene, either in the homozygous state or in compound heterozygosity with other loss-of-function mutations. The GAA expansio...

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Selected missense mutations impair frataxin processing in Friedreich ataxia

OBJECTIVE Frataxin (FXN) is a highly conserved mitochondrial protein. Reduced FXN levels cause Friedreich ataxia, a recessive neurodegenerative disease. Typical patients carry GAA repeat expansions on both alleles, while a subgroup of patients carry a missense mutation on one allele and a GAA repeat expansion on the other. Here, we report that selected disease-related FXN missense mutations imp...

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ژورنال

عنوان ژورنال: The American Journal of Human Genetics

سال: 2001

ISSN: 0002-9297

DOI: 10.1086/321283