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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10.1002/ana.25048

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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

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 › peer-review

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.

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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.",

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AU - Hattori, Nobutaka

AU - Follett, Jordan

AU - Rajput, Alex

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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.

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ER -

DNAJC12 and dopa-responsive nonprogressive parkinsonism

Abstract

Keywords

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