Analysis of the trinucleotide repeat expansion in Italian families affected with Huntington’s disease

150 subjects affected with HD and 45 at high risk for the disease were typed for the CAG trinucleotide repeat at the 5' end of IT15. In all of them we find expanded segments showing marked instability upon transmission. Their length distribution matches those previously reported and inversely correlates (-0.686) with age at onset. Two at risk sibs from a large HD pedigree show expanded segments that overlap the normal distribution and can represent reductions from the HD to the normal range. A case of instability on a normal chromosome is also reported. Finally, an analysis of the CAG repeat as a function of three polymorphic DNA markers at D4S127 and D4S95 loci shows no significant difference in the average repeat length on HD chromosomes grouped according to the cosegregating allele of each marker or to the corresponding haplotype. Despite the marked heterogeneity in repeat length among HD families, haplotypes are not associated with different values around which the repeat length fluctuates.