Abstract
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.
Original language | English |
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Pages (from-to) | 640-646 |
Number of pages | 7 |
Journal | Annals of Neurology |
Volume | 82 |
Issue number | 4 |
DOIs | |
Publication status | Published - Oct 2017 |
Keywords
- Adult
- Amyloid beta-Peptides
- Antiparkinson Agents
- Biogenic Amines
- Brain
- DNA Mutational Analysis
- DNA-Binding Proteins
- Family Health
- Female
- Humans
- Levodopa
- Male
- Middle Aged
- Mutation
- Parkinsonian Disorders
- Phenylalanine
- Repressor Proteins
- Sequestosome-1 Protein
- Young Adult
- alpha-Synuclein
- tau Proteins
- Journal Article