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GENATLAS PHENOTYPE
last update : 23-05-2017
Symbol PARK9
Location 1p36.13
Name Parkinson disease 9
Other name(s) dementia and supranuclear upgaze paresis, Kufor-Rakeb syndrome
Corresponding gene ATP13A2
Other symbol(s) DPP, KRS
Main clinical features
  • Parkinson disease, juvenile form, pallidopyramidal degeneration with supranuclear upgaze, levodopa responsive parkinsonism
  • onset between 11 and 16 years by a mast-like face, rigidity, bradykinesia without intention tremor and a rapid progression, spasticity, supranuclear upgaze paresis, and dementia
  • early onset levodopa-responsive dystonia-parkinsonism with pyramidal signs and eye movement abnormalities
  • brain MRI revealed generalized atrophy and putaminal and caudate iron accumulation bilaterally
    • Genetic determination autosomal recessive
    Function/system disorder neurology
    Type disease
    Mechanism(s)
    Gene mutationChromosome rearrangementEffectComments
    frameshift   abnormal protein/loss of function the unstable truncated mutants were retained in the endoplasmic reticulum and degraded by the proteasome
    Remark(s)
  • mislocalization of the mutant ATP13A2, resultant ER stress, alterations in the proteasomal pathways and premature degradation of mutant ATP13A2 mRNA contribute to the aetiology of PARK9 (PMID: 21542062))
  • ATP13A2 mutations may compromise protein function, disrupting cell cation balance and rendering cells prone to apoptosis (PMID: 22117566))
  • loss of ATP13A2 in fibroblasts from patients with Kufor-Rakeb syndrome leads to impaired lysosomal degradation capacity, resulting in accumulation of SNCA and toxicity in primary cortical neurons (PMID: 22442086))
  • lysosome abnormality is very likely to be the primary cause of KRS/PARK9 (PMID: 2349937)
  • mutations lead to several lysosomal alterations, including reduced proteolytic processing of cathepsin D (PMID: 27770614))