DNAJC6 Mutations Disrupt Dopamine Homeostasis in Juvenile Parkinsonism-Dystonia.
Joanne NgElisenda Cortès-SaladelafontLucia AbelaPichet TermsarasabKshitij MankadSniya SudhakarKathleen M GormanSimon J R HealesSimon PopeLorenzo BiassoniBarbara CsányiJohn CainKarl RakshiHelen CouttsSandeep JayawantRosalind JeffersonDeborah HughesÀngels García-CazorlaDetelina GrozevaF Lucy RaymondBelén Pérez-DueñasChristian De GoedeToni S PearsonEsther MeyerManju A KurianPublished in: Movement disorders : official journal of the Movement Disorder Society (2020)
DNAJC6 is an emerging cause of recessive juvenile parkinsonism-dystonia. DNAJC6 encodes the cochaperone protein auxilin, involved in CME of synaptic vesicles. The observed dopamine dyshomeostasis in patients is likely to be multifactorial, secondary to auxilin deficiency and/or neurodegeneration. Increased patient CSF cyclin G-associated kinase, in tandem with reduced auxilin levels, suggests a possible compensatory role of cyclin G-associated kinase, as observed in the auxilin knockout mouse. DNAJC6 parkinsonism-dystonia should be considered as a differential diagnosis for pediatric neurotransmitter disorders associated with low homovanillic acid levels. Future research in elucidating disease pathogenesis will aid the development of better treatments for this pharmacoresistant disorder. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Keyphrases
- deep brain stimulation
- parkinson disease
- early onset
- end stage renal disease
- drug induced
- cell cycle
- ejection fraction
- newly diagnosed
- chronic kidney disease
- uric acid
- protein kinase
- prefrontal cortex
- case report
- tyrosine kinase
- peritoneal dialysis
- current status
- autism spectrum disorder
- cell proliferation
- small molecule
- protein protein
- wild type