title: [A Parkin gene (PARK 2) and Parkinson's disease].
abstract: We identified a PARK 2 (AR-JP) family with a patient presenting with homozygous deletion of D 6 S305--a marker within the 17cM region for PARK 2 locus. Markers surrounding D 6 S305 which are mapped 0 cM apart from D 6 S305, were not deleted, indicating that PARK 2 gene is located extremely close to D 6 S305. Exon search in the inserts with average size of 100 kb of BAC clones, which harbor D 6 S305, led us to find the exonic sequences which was subsequently proved to be exon 7 of the Parkin gene. From this exon sequences, full-length cDNA was isolated, and BAC contig covering Parkin gene was generated. Homozygous deletions or frame-shift mutations in the Parkin gene were found in the patients with AR-JP/PARK 2, revealing that a loss-of-function of Parkin gene is responsible for AR-JP/PARK 2. Our findings indicate that constant production of Parkin protein is essentially required for maintaining the survival of nigral neurons. One attractive hypothesis is that Parkinson's disease and AR-JP/PARK 2 might share a common effector pathway for nigral neuronal death. In this scenario, as PARK 2 is not accompanied with Lewy body formation. Parkin might act at or downstream of synuclein aggregation, which has been recently implicated as a trigger event for neuronal death in Parkinson's disease. In any case, identification of functional targets of Parkin protein will give us an important clue to identify downstream events of neuronal death which is activated by inclusion body formation.
authors.affiliation: Department of Neurology, Juntendo University School of Medicine.
authors.forename: H
authors.initials: H
authors.lastname: Matsumine
mesh_terms: D016923:Cell Death; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D004298:Dopamine / Q000172:deficiency; D005091:Exons; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons; D010300:Parkinson Disease / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D017384:Sequence Deletion; D051843:Synucleins
chemical_list: D009419:Nerve Tissue Proteins; D011506:Proteins; D051843:Synucleins; D004298:Dopamine