title: Early onset parkinsonism with diurnal fluctuation maps to a locus for juvenile parkinsonism.
abstract: Early onset parkinsonism with diurnal fluctuation (EPDF) is a dopa-responsive parkinsonism characterized by early onset and improvement of parkinsonian symptoms after sleep. A pathologic study of one case of EPDF 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 and analyzed 151 meioses. Multipoint linkage analysis gave a peak lod score of 14.2 at 1.0 cM telomeric to D6S305 and placed the disease locus in the 17-cM interval between D6S437 and D6S253, which is exactly the 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 nonconsanguinity (8/17 families), the absence of commonly shared haplotypes, and the widespread geographic distribution of the families' origins suggest that EPDF has multiple founder mutations. The authors concluded that EPDF and ARJP are allelic disorders and should be included in the spectrum of a single-clinicogenetic entity of chromosome 6q-linked parkinsonism. This disease could be characterized by a benign clinical course and relatively selective degeneration of nigral dopaminergic 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.
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Matsumine
authors.forename: Y
authors.initials: Y
authors.lastname: Yamamura
authors.forename: T
authors.initials: T
authors.lastname: Kobayashi
authors.forename: S
authors.initials: S
authors.lastname: Nakamura
authors.forename: S
authors.initials: S
authors.lastname: Kuzuhara
authors.forename: Y
authors.initials: Y
authors.lastname: Mizuno
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D002940:Circadian Rhythm / Q000502:physiology*; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D008126:Lod Score; D010300:Parkinson Disease / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype