AUTOSOMAL RECESSIVE JUVENILE PARKINSONISM MAPS TO 6Q25.2-Q27 IN 4 ETHNIC-GROUPS - DETAILED GENETIC-MAPPING OF THE LINKED REGION

Parkinson disease (PD) is a common neurodegenerative condition associa ted with degeneration of dopaminergic neurons in the zona compacta of the substantia nigra. There is increasing evidence that genetic factor s play a role in the etiology of PD, although genetic heterogeneity is likely. An autosomal dominant syndrome with many similarities to spor adic PD has been mapped to 4q21-22 in a large Italian pedigree and has been found to be due to mutation of the alpha-synuclein gene. However , this gene appears to account for only a minority of PD, and a suscep tibility locus for autosomal dominant parkinsonism has recently been m apped, on 2p13. Autosomal recessive juvenile parkinsonism (JP), which shows marked clinical similarity to PD, maps to 6q25.2-q27. We found l inkage to this region in a group of 15 families from four distinct eth nic backgrounds. A full genomic screen excluded other candidate region s. We have constructed a detailed genetic map of the linked region and have mapped the position of the manganese superoxide dismutase gene ( SOD2). Recombination events restricted the JP locus to a 6.9-cM region and excluded SOD2. The apparent homozygosity for null alleles at D6S9 55 in one family suggested a deletion and finer localization of the JP locus.