LOCALIZATION OF A GENE FOR AN AUTOSOMAL RECESSIVE FORM OF JUVENILE PARKINSONISM TO CHROMOSOME 6Q25.2-27

An autosomal recessive form of juvenile Parkinsonism (AR-JP) (MIM 6001 16) is a levodopa-responsive Parkinsonism whose pathological finding i s a highly selective degeneration of dopaminergic neurons in the zona compacta of the substantia nigra. By linkage analysis of diallelic pol ymorphism of the Mn-superoxide dismutase gene (SOD2), we found a famil y with AR-JP showing perfect segregation of the disease with the SOD2 locus. By extending the linkage analysis to 13 families with AR-JP, we discovered strong evidence for the localization of the AR-JP gene at chromosome 6q25.2-27, including the SOD2 locus, with the maximal cumul ative pairwise LOD scores of 7.26 and 7.71 at DGS305 (theta=.03) and D 6S253 (theta=.02), respectively. Observation of obligate recombination events, as well as multipoint linkage analysis, placed the AR-JP gene in a 17-cM interval between D6S437 and D6S264. Delineation of the AR- JP gene will be an important step toward our understanding of the mole cular mechanism underlying selective degeneration of the nigral neuron s.