the genetic analysis of iranian patients with huntingtons disease

huntingtons disease (hd) is an autosomal dominant inherited disease characterized by involuntary movements, behavioral and personality changes, dementia and cognitive decline. although the mean age of onset is about 40 years, it varies from 5 to 79 years. therefore, at-risk individuals are never sure to have escaped the disease. hd is a member of the growing family of neurodegenerative disorders associated with trinucleotide repeat expansion. the genetic defect is a cag trinucleotide repeat expansion in exon 1 of the it15 gene on chromosome 4, resulting in an enlarged polyglutamine tract in the huntigtin protein. in unaffected individuals, the repeat length ranges from 9 to 34 with a median range of 19. expansion of a cag repeat beyond the critical threshold of 36 repeats results in the disease and forms the basis of pcr-based genetic tests. in this study, we analyzed 25 patients with clinical diagnosis of hd and 30 normal controls. the cag repeat numbers varied from 38 to 51 (median: 43) in hd patients, while individuals of the normal control group had 10-36 cag repeat numbers (median: 20). dna analysis showed expansion of the (cag)n repeat in 15 hd patients. our results showed that not all patients with the hd phenotype carried the expansion at the it15 gene. furthermore, reaching molecular diagnosis was impossible in all individuals since some alleles of the intermediate size were found.