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 Rajput; Stefano Duga

doi:10.1002/ana.25048

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 journal › Article › peer-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 language	English
Pages (from-to)	640-646
Number of pages	7
Journal	Annals of Neurology
Volume	82
Issue number	4
DOIs	https://doi.org/10.1002/ana.25048
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

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Straniero, L., Guella, I., Cilia, R., Parkkinen, L., Rimoldi, V., Young, A., Asselta, R., Soldà, G., Sossi, V., Stoessl, A. J., Priori, A., Nishioka, K., Hattori, N., Follett, J., Rajput, A., Blau, N., Pezzoli, G., Farrer, M. J., Goldwurm, S., ... Duga, S. (2017). DNAJC12 and dopa-responsive nonprogressive parkinsonism. Annals of Neurology, 82(4), 640-646. https://doi.org/10.1002/ana.25048

Straniero, L, Guella, I, Cilia, R, Parkkinen, L, Rimoldi, V, Young, A, Asselta, R , Soldà, G, Sossi, V, Stoessl, AJ, Priori, A, Nishioka, K, Hattori, N, Follett, J, Rajput, A, Blau, N, Pezzoli, G, Farrer, MJ, Goldwurm, S, Rajput, AH & Duga, S 2017, 'DNAJC12 and dopa-responsive nonprogressive parkinsonism', Annals of Neurology, vol. 82, no. 4, pp. 640-646. https://doi.org/10.1002/ana.25048

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title = "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.",

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",

author = "Letizia Straniero and Ilaria Guella and Roberto Cilia and Laura Parkkinen and Valeria Rimoldi and Alexander Young and Rosanna Asselta and Giulia Sold{\`a} and Vesna Sossi and Stoessl, {A Jon} and Alberto Priori and Kenya Nishioka and Nobutaka Hattori and Jordan Follett and Alex Rajput and Nenad Blau and Gianni Pezzoli and Farrer, {Matthew J} and Stefano Goldwurm and Rajput, {Ali H} and Stefano Duga",

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year = "2017",

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doi = "10.1002/ana.25048",

language = "English",

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AU - Straniero, Letizia

AU - Guella, Ilaria

AU - Cilia, Roberto

AU - Parkkinen, Laura

AU - Rimoldi, Valeria

AU - Young, Alexander

AU - Asselta, Rosanna

AU - Soldà, Giulia

AU - Sossi, Vesna

AU - Stoessl, A Jon

AU - Priori, Alberto

AU - Nishioka, Kenya

AU - Hattori, Nobutaka

AU - Follett, Jordan

AU - Rajput, Alex

AU - Blau, Nenad

AU - Pezzoli, Gianni

AU - Farrer, Matthew J

AU - Goldwurm, Stefano

AU - Rajput, Ali H

AU - Duga, Stefano

PY - 2017/10

Y1 - 2017/10

N2 - 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.

AB - 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.

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KW - Amyloid beta-Peptides

KW - Antiparkinson Agents

KW - Biogenic Amines

KW - Brain

KW - DNA Mutational Analysis

KW - DNA-Binding Proteins

KW - Family Health

KW - Female

KW - Humans

KW - Levodopa

KW - Male

KW - Middle Aged

KW - Mutation

KW - Parkinsonian Disorders

KW - Phenylalanine

KW - Repressor Proteins

KW - Sequestosome-1 Protein

KW - Young Adult

KW - alpha-Synuclein

KW - tau Proteins

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DO - 10.1002/ana.25048

M3 - Article

C2 - 28892570

VL - 82

SP - 640

EP - 646

JO - Annals of Neurology

JF - Annals of Neurology

SN - 0364-5134

IS - 4

ER -

DNAJC12 and dopa-responsive nonprogressive parkinsonism

Abstract

Keywords

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