The diagnosis of Friedreich ataxia is based on the clinical symptoms and GAA repeats expansions. In our experience, checking FXN gene exons for mutations along with GAA repeat analysis may give better clue for its diagnosis. In the present study, total 49 suspected Friedreich ataxia patients were analyzed for GAA repeat expansion. Eleven patients have normal number of GAA repeats, thereby termed as FRDA negative patients. Thirty-eight patients showed no amplification using GAA repeat analysis. Since no conclusion was possible based on these results, these patients were designated as uninformative. We have analyzed 5 exons of the FXN gene in FRDA negative and uninformative patients to check for possible mutations. It was observed that there were no mutations found in any of FRDA negative and most uninformative patients. We further used long range PCR to check for deletion of exon 5a. It was found that 18 patients showed expression for exon 5a PCR but none in long range PCR. Five patients showed no expression for exon 5a PCR as well as long range PCR indicating that these 5 patients may be positive FRDA patients. These findings need to be correlated with clinical history of these patients for confirmation. 1. Introduction Friedreich ataxia (FRDA) is an autosomal recessively inherited neurodegenerative disease, caused due to expansion of the intronic GAA trinucleotide repeats or mutations in the FXN gene on chromosome 9q13 [1, 2]. The FXN gene consists of seven exons—1, 2, 3, 4, 5a, 5b, and 6. Frataxin, a highly conserved 210 amino acid protein with functions in iron-sulfur cluster biosynthesis, is produced by expression of exons 1–5a [1–6]. The gene FXN contains a GAA trinucleotide repeat in the first intron. The size range of the repeat is between 6 and 34 repeats in the wild-type gene [1, 7]. An expansion of the repeat in disease conditions increases the repeat size to 66–1700 or more repeats [1, 7]. It affects the expression of the gene, resulting in the reduced levels of frataxin mRNA and protein [3, 8]. Formation of sticky DNA, DNA-RNA hybrid, and epigenetic changes are the proposed mechanisms for disruption of FXN gene expression [9–11]. Most cases of FRDA are homozygous having expansion of the GAA trinucleotide repeat in the first intron of the FXN gene, whereas few cases can be heterozygous, in which there is GAA expansion in one allele and point mutation or deletion in the other allele of FXN gene [1, 2]. The onset of FRDA is usually before 25 years of age [1, 12]. However, the diseaseonset after 25 years of age is known as late onset Friedreich
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