ANALYSIS OF TRINUCLEOTIDE REPEAT EXPANSIO N AS A NEW MECHANISM OF MUTATION IN HUNTINGTONS-CHOREA - THEORETICAL AND APPLIED ASPECTS

The Huntington's chorea mutation consists of expansion of trinucleotid e CAG repeats in the recently discovered gene IT-15. In this work, for the first time in a population of Russian patients, correlations betw een the number of copies of CAG repeats and various clinical character istics of the disease are investigated. It is established that the deg ree of triplet expansion determines the age of onset of the disease an d the rate of progression of the neurological and mental symptoms of H untington's chorea, and it is also shown that the genetic instability of the mutant allele is considerably higher upon transmission of the d isease gene along the paternal line. We obtained direct confirmation o f the possibility of genetic instability of a normal allele inherited paternally. In this work, the first successful direct (including precl inical) DNA diagnosis in Russia of Huntington's chorea was obtained.