molecular analysis of the (cag)n repeat causing huntingtons disease in 66 iranian families

huntington’s disease (hd) is an inherited neurodegenerative disorder characterized by chorea and progressive dementia. the mutation causing the disease has been identified as an unstable expansion of a tri-nucleotide (cag) n at the 5 end of the it 15 gene on chromosome 4. we analyzed the distribution of cag repeats in 66 iranian patients belonging to 66 unrelated families. we found one expanded cag allele in 37 patients (56%). in these hd patients, expanded alleles varied from 40 to 83 cag units and normal alleles varied from 13 to 36 cags. a significant negative correlation was found between age at onset of symptoms and size of the expanded cag allele (r=- 0.51 p=0.1). in addition, we genotyped 25 unrelated control individuals (a total of 50 alleles) and found normal cag repeats varying from 10 to 34 units. in conclusion, our results showed that molecular confirmation of the clinical diagnosis in hd should be sought in all suspected patients, making it possible for adequate genetic counseling. this study is the first report on molecular diagnosis of huntingtons disease among iranian population and ever in the middle east in spite of the high frequency of consanguineous marriages in this region. we suggest that huntington like diseases should be investigated for those patients who are negative for expansion.