CHROMOSOME 6-LINKED AUTOSOMAL RECESSIVE EARLY-ONSET PARKINSONISM - LINKAGE IN EUROPEAN AND ALGERIAN FAMILIES, EXTENSION OF THE CLINICAL SPECTRUM, AND EVIDENCE OF A SMALL HOMOZYGOUS DELETION IN ONE FAMILY

The gene for autosomal recessive juvenile Parkinsonism (AR-JP) recentl y has been mapped to chromosome 6q25.2-27 in Japanese families. We hav e tested one Algerian and 10 European multiplex families with early-on set Parkinson disease for linkage to this locus, with marker D6S305. H omogeneity analysis provided a conditional probability in favor of lin kage of >.9 in eight families, which were analyzed further with eight microsatellite markers spanning the 17-cM AR-JP region. Haplotype reco nstruction for eight families and determination of the smallest region of homozygosity in two consanguineous families reduced the candidate interval to 11.3 cM. If the deletion of two microsatellite markers (D6 S411 and D6S1550) that colocalize on the genetic map and that segregat e with the disease in the Algerian family is taken into account, the c andidate region would be reduced to <1 cM. These findings should facil itate identification of the corresponding gene. We have confirmed link age of AR-JP, in European families and in an Algerian family, to the P ARK2 locus. PARK2 appears to be an important locus for AR-JP in Europe an patients. The clinical spectrum of the disease in our families, wit h age at onset less than or equal to 58 years and the presence of pain ful dystonia in some patients, is broader than that reported previousl y.