Abnormal gene product identified in hereditary dentatorubral–pallidoluysian atrophy (DRPLA) brain

Abstract
Dentatorubral-pallidoluysian atrophy (DRPLA) is associated with the expansion of an unstable CAG repeat. Using antibodies against a synthetic peptide corresponding to the sequence of the DRPLA gene product C terminus, we have identified the DRPLA gene product in normal human brains as a approximately 190 kD protein. We also find a larger approximately 205 kD protein specifically in DRPLA brains. Immunohistochemically, the DRPLA gene product is observed mainly in the neuronal cytoplasm. Our results demonstrate the existence of the expanded CAG repeat gene product and support the possibility that the expanded CAG-encoded polyglutamine stretch may participate in the pathological process of the similar trinucleotide repeat diseases.