[Investigation of exon 1 in FXN gene in patients with clinical symptomatic of friedreich ataxia]

ABSTRACT

Friedreich's ataxia [FRDA] is an autosomal recessive disorder that is typically associated with dysarthria, muscle weakness, spasticity in the lower limbs, scoliosis, bladder dysfunction, absent lower limb reflexes, and loss of position and vibration sense. Approximately two-thirds of these patients suffer from cardiomyopathy and more than 30% have diabetes mellitus. Individuals with FRDA have identifiable mutations in the FXN gene. The most common type of mutation which is observed on both alleles in more than 98% of patients is an expansion of a GAA triplet-repeat in intron of FXN gene. Approximately 2% of individuals with FRDA are compound heterozygotes, who have a GAA expansion in the disease-causing range in one FXN allele and an inactivating FXN mutation in another allele. Aim of the present study was to investigate exon 1 in FRDA gene in patients with clinical symptoms of Friedreich's Ataxia that have not GAA triplet-repeat expansion in intron 1 of FXN gene. In this study, exon 1 in 5 patients suspected of FRDA analyzed using PCR and sequencing. An A to G transition at nucleotide number 815284, in exon 1 was observed in all patients. The results of this study showed that disease-causing homozygous mutations could be because of consanguinity marriage in Iran. Therefore, sequencing of all exons of the gene is necessary