A. Novelletto et al., ANALYSIS OF THE TRINUCLEOTIDE REPEAT EXPANSION IN ITALIAN FAMILIES AFFECTED WITH HUNTINGTON DISEASE, Human molecular genetics, 3(1), 1994, pp. 93-98
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 tran
smission. 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 norm
al 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 polymor
phic DNA markers at D4S127 and D4S95 loci shows no significant differe
nce in the average repeat length on HD chromosomes grouped according t
o the cosegregating allele of each marker or to the corresponding hapl
otype. Despite the marked heterogeneity in repeat length among HD fami
lies, haplotypes are not associated with different values around which
the repeat length fluctuates.