DNAJC12 and dopa-responsive nonprogressive parkinsonism.

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.

• Authors: Letizia Straniero, Ilaria Guella, Roberto Cilia, Laura Parkkinen, Valeria Rimoldi, Alexander Young, Rosanna Asselta, Giulia Soldà, Vesna Sossi, A Jon Stoessl, Alberto Priori, Kenya Nishioka, Nobutaka Hattori, Jordan Follett, Alex Rajput, Nenad Blau, Gianni Pezzoli, Matthew J Farrer, Stefano Goldwurm, Ali H Rajput, Stefano Duga
• Journal: Annals of neurology (Ann Neurol) Vol. 82 Issue 4 Pg. 640-646 (Oct 2017) ISSN: 1531-8249 [Electronic] United States
• PMID: 28892570 (Publication Type: Journal Article)
• Copyright: © 2017 American Neurological Association.

Chemical References

• Amyloid beta-Peptides
• Antiparkinson Agents
• Biogenic Amines
• DNA-Binding Proteins
• DNAJC12 protein, human
• Repressor Proteins
• SQSTM1 protein, human
• Sequestosome-1 Protein
• TARDBP protein, human
• alpha-Synuclein
• tau Proteins
• Levodopa
• Phenylalanine

Topics

• Adult
• Amyloid beta-Peptides (metabolism)
• Antiparkinson Agents (therapeutic use)
• Biogenic Amines (metabolism)
• Brain (metabolism, pathology)
• DNA Mutational Analysis
• DNA-Binding Proteins (metabolism)
• Family Health
• Female
• Humans
• Levodopa (therapeutic use)
• Male
• Middle Aged
• Mutation (genetics)
• Parkinsonian Disorders (drug therapy, genetics, pathology)
• Phenylalanine (metabolism)
• Repressor Proteins (genetics)
• Sequestosome-1 Protein (metabolism)
• Young Adult
• alpha-Synuclein (metabolism)
• tau Proteins (metabolism)