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Ann Neurol. 2017 Oct;82(4):640-646. doi: 10.1002/ana.25048. Epub 2017 Oct 11.

DNAJC12 and dopa-responsive nonprogressive parkinsonism.

Author information

1
Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.
2
Centre for Applied Neurogenetics, University of British Columbia, Vancouver, BC, Canada.
3
Parkinson Institute, ASST "Gaetano Pini-CTO", Milan, Italy.
4
Nuffield Department of Clinical Neurosciences, Oxford Parkinson's Disease Centre, University of Oxford, Oxford, United Kingdom.
5
Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
6
Pacific Parkinson's Research Centre & Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada.
7
"Aldo Ravelli" Research Center for Neurotechnology and Experimental Brain Therapeutics, Department of Health Sciences, University of Milan & ASST Santi Paolo e Carlo, Milan, Italy.
8
Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
9
Division of Neurology, Saskatchewan Movement Disorders Program, University of Saskatchewan, Royal University Hospital, Saskatoon, SK, Canada.
10
Dietmar-Hopp-Metabolic Center, Department of General Pediatrics, University Hospital, Heidelberg, Germany.

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.

PMID:
28892570
DOI:
10.1002/ana.25048
[Indexed for MEDLINE]

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