ABNORMAL GENE-PRODUCT IDENTIFIED IN HEREDITARY DENTATORUBRAL-PALLIDOLUYSIAN ATROPHY (DRPLA) BRAIN

Dentatorubral-pallidoluysian atrophy (DRPLA) is associated with the ex pansion of an unstable CAG repeat. Using antibodies against a syntheti c peptide corresponding to the sequence of the DRPLA gene product C te rminus, we have identified the DRPLA gene product in normal human brai ns as a approximate to 190 kD protein. We also find a larger approxima te to 205 kD protein specifically in DRPLA brains. Immunohistochemical ly, the DRPLA gene product is observed mainly in the neuronal cytoplas m. Our results demonstrate the existence of the expanded CAG repeat ge ne product and support the possibility that the expanded CAG-encoded p olyglutamine stretch may participate in the pathological process of th e similar trinucleotide repeat diseases.