DNAJC12 and dopa-responsive nonprogressive parkinsonism

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 RajputStefano Duga

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)640-646
Number of pages7
JournalAnnals of Neurology
Volume82
Issue number4
DOIs
Publication statusPublished - 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

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