identification and sizing of gaa trinucleotide repeat expansion, in iranian friedreich’s ataxia patients

friedreich’s ataxia (fa) is the commonest genetic cause of ataxia and is associated with the expansion of a gaa repeat in intron 1 of the frataxin gene. iron accumulation in the mitochondria of patients with fa results in hypersensitivity to oxidative stress. mitochondrial dna (mtdna) could be considered a candidate modifier factor for fa disease since mitochondrial oxidative stress is thought to be involved in the pathogenesis of this disease. we studied 137 iranian patients (50 females and 87 males) from 110 unrelated families. dna from each patient was extracted and frequency and length of (gaa) n repeat was analyzed using a long-range polymerase chain reaction (pcr) test. also, we investigated the impact of gaa size on neurological findings, age of onset and disease development. homozygous gaa expansion was found in 101 (73%) cases. in four cases (27%), no expansion was observed that resulted in ruling out the diagnosis of friedreich’s ataxia. in cases with gaa expansions, ataxia, scoliosis and pes cavus, cardiac abnormalities and some neurological findings occurred more frequently than in our patients without gaa expansion. molecular analysis was imperative for the diagnosis of friedreich’s ataxia, not only for typical cases but also for atypical ones. diagnosis based on clinical findings is limited, however, it aids in better screening of suspected cases that should receive genetically evaluated.