Park9 -Linked Parkinsonism in Eastern Asia: Mutation Detection in Atp13a2 and Clinical Phenotype

PARK9, a form of autosomal recessive parkinsonism, or Kufor-Rakeb syndrome (KRS), is characterized by subacute or slowly progressive, juvenile-onset, levodopa-responsive parkinsonism, pyramidal signs, dementia, and supranuclear gaze palsy.1–5 Recently, ATP13A2 was identified as the causative gene for PARK9 in Chilean and Jordanian families.4 This gene contains 29 exons encoding a lysosomal type 5 P-type ATPase. Six mutations have been reported in only five probands so far.4,5 Here, we describe a Japanese patient with KRS with a novel mutation who developed early onset parkinsonism, dementia, and other features. We also describe PET findings of PARK9 -linked parkinsonism. ### Methods. Haplotype analysis was conducted in 117 (mainly Japanese) patients with early onset (≤50, 26.8 ± 11.7 years, mean ± SD) parkinsonism. Among them, 14 patients had dementia. Patients who exhibited homozygosity on PARK9 locus by haplotype analysis underwent direct sequencing for all 29 exons (e-Methods on the Neurology ® Web site at www.neurology.org); the remaining patients underwent direct sequencing for exons 13, 16, and 26, in which mutations …