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

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

Access to Document

10.1002/ana.25048

Fingerprint Dive into the research topics of 'DNAJC12 and dopa-responsive nonprogressive parkinsonism'. Together they form a unique fingerprint.

Cite this

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

DNAJC12 and dopa-responsive nonprogressive parkinsonism. / Straniero, Letizia; Guella, Ilaria; Cilia, Roberto; Parkkinen, Laura; Rimoldi, Valeria; Young, Alexander; Asselta, Rosanna ; Soldà, Giulia; Sossi, Vesna; Stoessl, A Jon; Priori, Alberto; Nishioka, Kenya; Hattori, Nobutaka; Follett, Jordan; Rajput, Alex; Blau, Nenad; Pezzoli, Gianni; Farrer, Matthew J; Goldwurm, Stefano; Rajput, Ali H; Duga, Stefano.

In: Annals of Neurology, Vol. 82, No. 4, 10.2017, p. 640-646.

Research output: Contribution to journal › Article

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

Straniero, Letizia ; Guella, Ilaria ; Cilia, Roberto ; Parkkinen, Laura ; Rimoldi, Valeria ; Young, Alexander ; Asselta, Rosanna ; Soldà, Giulia ; Sossi, Vesna ; Stoessl, A Jon ; Priori, Alberto ; Nishioka, Kenya ; Hattori, Nobutaka ; Follett, Jordan ; Rajput, Alex ; Blau, Nenad ; Pezzoli, Gianni ; Farrer, Matthew J ; Goldwurm, Stefano ; Rajput, Ali H ; Duga, Stefano. / DNAJC12 and dopa-responsive nonprogressive parkinsonism. In: Annals of Neurology. 2017 ; Vol. 82, No. 4. pp. 640-646.

@article{826d66c8d6374782bda7be154cd73e0e,

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",

note = "{\textcopyright} 2017 American Neurological Association.",

year = "2017",

month = oct,

doi = "10.1002/ana.25048",

language = "English",

volume = "82",

pages = "640--646",

journal = "Annals of Neurology",

issn = "0364-5134",

publisher = "John Wiley and Sons Inc.",

number = "4",

}

TY - JOUR

T1 - DNAJC12 and dopa-responsive nonprogressive parkinsonism

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.

KW - Adult

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

KW - Journal Article

U2 - 10.1002/ana.25048

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 -