EARLY-ONSET PARKINSONISM WITH DIURNAL FLUCTUATION MAPS TO A LOCUS FORJUVENILE PARKINSONISM

Early onset parkinsonism with diurnal fluctuation (EPDF) is a dopa-res ponsive parkinsonism characterized by early onset and improvement of p arkinsonian symptoms after sleep. A pathologic study of one case of EP DF showed selective neuronal degeneration in the zona compacta of the substantia nigra without Lewy body formation. To determine the disease locus for EPDF, the authors examined 53 members of 17 EPDF families a nd analyzed 151 meioses. Multipoint linkage analysis gave a peak lod s core of 14.2 at 1.0 cM telomeric to D6S305 and placed the disease locu s in the 17-cM interval between D6S437 and D6S253, which is exactly th e same position mapped for autosomal recessive juvenile parkinsonism ( ARJP; Mendelian inheritance in man 600116). The highest two-point lod score was obtained at D6S305 (10.13 at theta = 0). Haplotype analysis agreed with the result of multipoint analysis. A high proportion of no nconsanguinity (8/17 families), the absence of commonly shared haploty pes, and the widespread geographic distribution of the families' origi ns suggest that EPDF has multiple founder mutations. The authors concl uded that EPDF and ARJP are allelic disorders and should be included i n the spectrum of a single-clinicogenetic entity of chromosome 6q-link ed parkinsonism. This disease could be characterized by a benign clini cal course and relatively selective degeneration of nigral dopaminergi c neurons with no Lewy body formation. To determine whether ARJP/EPDF constitutes a significant proportion of familial or sporadic forms of benign early onset parkinsonism will require further study.