Analysis of the (CAG)n repeat at the IT15 locus in a population from Calabria (southern Italy)

The defect causing Huntington's disease (HD) has recently been discovered as an expanded CAG trinucleotide repeat located at the 5' end of the IT15 gene. This discovery allows the molecular diagnosis of HD by measuring the CAG repeat length. The normal and pathological repeat ranges in a population need to be established before a diagnostic test for HD can be performed. To determine the distribution of IT15 alleles in a population from Calabria (southern Italy), we analyzed 102 normal subjects and 9 HD patients coming from a defined area of Calabria (province of Cosenza). Expanded alleles ranged from 44 to 76 repeats. Normal alleles varied from 8 to 27 repeats, which is one of the lowest values observed at the top of the normal range; the mean was significantly different from the value observed in six other populations. The allele distribution seemed to group mainly around the mode, and no intermediate alleles were present in our sample. These results suggest a particular stability of the CAG repeat at the IT15 locus in the Calabrian group and confirm once again the peculiar genetic structure of this population.