Differential expression of the parkin gene in the human brain and peripheral leukocytes.

Molecular cloning of the responsible gene on chromosome 6q25.2-27 for autosomal recessive juvenile parkinsonism (AR-JP) identified a novel protein of unknown function, named parkin. In patients with AR-JP, deletions most commonly involve exons 3-5 in the parkin gene. For mutation screening we tried to analyze the parkin transcript amplified by RT-PCR. Based on the assumption that illegitimate transcription of the parkin gene may occur in every cell type, we successfully amplified the parkin message from human peripheral leukocytes using RT-PCR. The parkin transcript in leukocytes was smaller in size than the full-length transcript in the brain. DNA sequencing determined that exons 3-5 were spliced out in the normal human leukocyte transcript. Our results demonstrate that alternative splicing produces distinct parkin transcripts in different tissues. Moreover, physiological splicing of deletion-prone exons may provide an important clue to understanding the pathogenesis of AR-JP.