STABILITY OF THE HUNTINGTON-DISEASE (CAG)N REPEAT IN A LATE-ONSET FORM OCCURRING ON THE ISLAND OF CRETE

Huntington disease (HD) is an autosomal-dominant disorder of mid-life onset characterized by chorea, dementia, and oculomotor disturbances. Anticipation is commonly seen in HD families, particularly when the di sease is inherited through the father. The disorder is associated with an expanded (CAG)n repeat in the IT15 gene that is unstable and tends to increase in size during meiotic transmissions, particularly of pat ernal origin. We have detected an unusual form of HD on the island of Crete which has distinctly different characteristics. Data from eight families encompassing 48 HD patients, showed a median age at onset 15- 20 years later than that for HD occurring worldwide, There were nojuve nile cases and no anticipation, DNA analysis in 12 HD patients showed expansion of the (CAG)n repeat the size of which was identical among m embers of each family or varied by only one unit, The elongated DNA se gment was passed stably or contracted during both paternal and materna l transmissions thus indicating that unique molecular mechanisms may b e operational in this form of HD.