OBJECTIVE: To describe a novel dinucleotide deletion in the FRDA gene in two Malaysian siblings with FRDA1.
SETTING: Tertiary referral university hospital setting.
PATIENTS AND METHODS: A previously healthy 10-year-old Malaysian boy, presented with fever, lethargy, headaches, dysarthria, dysphagia, vertigo and ataxia which developed over a one week period. His neurological exam revealed evidence of dysarthria and ataxia, mild generalized weakness and choreoform movements of the tongue and hands. His reflexes were absent and Babinski sign was present bilaterally. A nine-year-old sister was found to have mild ataxia but was otherwise neurologically intact.
RESULTS: Molecular genetic studies demonstrated that both siblings were compound heterozygotes with a GAA expansion on one allele and a novel dinucleotide deletion on the other allele.
CONCLUSIONS: We describe a novel dinucleotide deletion in the first exon of the FRDA gene in two siblings with FRDA1. Additionally this is the first report of FRDA1 occurring in a family of southeast Asian descent, it demonstrates intrafamilial phenotypic variability, and confirms that atypical phenotypes are associated with compound heterozygosity.
METHODS: A number of 22 Iranian patients (8 females and 14 males) from 16 unrelated families were studied. DNA was extracted from the peripheral blood of patients. The frequency and length of (GAA)n repeats in intron 1 of the FXN gene were analyzed using long-range PCR. In this study, the clinical criteria of FRDA in our patients and the variability in their clinical signs were also demonstrated.
RESULTS: An inverse relationship was observed between GAA repeat size and the age of onset. Although some distinguishable clinical features (such as limb ataxia and lower limb areflexia) were found in our patients, 90-95% of them had extensor plantar response and dysarthria. The results showed only one positive diabetes patient and also different effects on eye movement abnormality among our patients.
CONCLUSION: The onset age of symptoms showed a significant inverse correlation with allele size in our patients (P>0.05). Based on comparisons of the clinical data of all patients, clinical presentation of FRDA in Iranian patients did not differ significantly from other FRDA patients previously reported.