DNAJC12 and dopa-responsive nonprogressive parkinsonism.
Letizia StranieroIlaria GuellaRoberto CiliaLaura ParkkinenValeria RimoldiAlexander YoungRosanna AsseltaGiulia SoldàVesna SossiA Jon StoesslAlberto PrioriKenya NishiokaNobutaka HattoriJordan FollettAlex RajputNenad BlauGianni PezzoliMatthew J FarrerStefano GoldwurmAli H RajputStefano DugaPublished in: Annals of neurology (2017)
Biallelic DNAJC12 mutations were described in children with hyperphenylalaninemia, neurodevelopmental delay, and dystonia. We identified DNAJC12 homozygous null variants (c.187A>T;p.K63* and c.79-2A>G;p.V27Wfs*14) in two kindreds with early-onset parkinsonism. Both probands had mild intellectual disability, mild nonprogressive, motor symptoms, sustained benefit from small dose of levodopa, and substantial worsening of symptoms after levodopa discontinuation. Neuropathology (Proband-A) revealed no alpha-synuclein pathology, and substantia nigra depigmentation with moderate cell loss. DNAJC12 transcripts were reduced in both patients. Our results suggest that DNAJC12 mutations (absent in 500 early-onset patients with Parkinson's disease) rarely cause dopa-responsive nonprogressive parkinsonism in adulthood, but broaden the clinical spectrum of DNAJC12 deficiency. Ann Neurol 2017;82:640-646.
Keyphrases
- early onset
- intellectual disability
- parkinson disease
- late onset
- deep brain stimulation
- autism spectrum disorder
- single cell
- end stage renal disease
- drug induced
- young adults
- cancer therapy
- prognostic factors
- depressive symptoms
- cell therapy
- dna methylation
- high intensity
- physical activity
- mesenchymal stem cells
- peritoneal dialysis
- drug delivery
- gene expression
- early life
- replacement therapy