REDUCTION OF CAG EXPANSIONS IN CEREBELLAR CORTEX AND SPINAL-CORD OF DRPLA

Recent studies have identified an unstable expansion of a CAG repeat i n a gene located on chromosome 12 as a cause of dentatorubropallidoluy sian atrophy (DRPLA). To investigate whether the somatic heterogeneity may relate to the selective neuronal damage caused by the disease, ge nomic DNA from various tissues of an autopsied patient with DRPLA was examined to compare possible variations of expanded CAG repeats for th e disease. Although the size of the expanded CAG repeat from many orga ns was almost the same as that from peripheral lymphocytes, those from cerebellar cortex and spinal cord were unexpectedly reduced and numbe rs of peaks within an expanded allele were relatively strict. These re sults suggest that the CAG repeat is not simply expanded in the genome of the tissues that are most involved in DRPLA, but that another mech anism might be responsible for the specific neuronal death.