Journal Article

DZNE-2026-00169

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Rare but Relevant? Assessing Variants in Dystonia-Linked Genes in Parkinson's Disease.

Lange, L. M. ; Fang, Z.-H.DZNE* ; Screven, L. ; Tan, A. H. ; Alcalay, R. N. ; Amouri, R. ; Bovenzi, R. ; Fenn, M. ; Frost, J. L. I. ; Jankovic, J. ; Jasaityte, S. ; Jaunmuktane, Z. ; Jeon, B. ; Sarmiento, I. J. K. ; Krüger, R. ; Kuhlenbäumer, G. ; Lin, C.-H. ; Pavelka, L. ; Periñan, M. T. ; Sassi, S. B. ; Schirinzi, T. ; Shin, J. H. ; Shulman, J. M. ; Tay, Y. W. ; Uitti, R. ; Warner, T. ; Wszolek, Z. K. ; Wu, L. ; Wu, R.-M. ; Zeuner, K. E. ; Blauwendraat, C. ; Singleton, A. ; Mencacci, N. E. ; Morris, H. R. ; Lim, S.-Y. ; Lohmann, K. ; Klein, C. ; Program, G. P. G. (Collaboration Author)

2026
Wiley New York, NY

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Please use a persistent id in citations: doi:10.1002/mds.70073

Abstract: Dystonia and Parkinson's disease (PD) exhibit clinical and genetic overlap, but the relevance of dystonia gene variants in PD remains unclear.The aim was to assess the frequency of dystonia-linked pathogenic variants in PD.We screened sequencing data from 15,684 individuals (8272 PD, 3200 atypical parkinsonism, and 4212 unaffected) from the Global Parkinson's Genetics Program (GP2) and Accelerating Medicines Partnership-Parkinson's Disease (AMP-PD) for variants in genes linked to isolated dystonia, dystonia-parkinsonism, and myoclonus-dystonia.Pathogenic variants were identified only in PD patients. Forty-five PD individuals (0.54%) carried 26 distinct (likely) pathogenic variants in nine dystonia-linked genes, most frequently in GCH1, followed by VPS16.Though rare, pathogenic variants in dystonia-linked genes are present in clinically and pathologically diagnosed PD. Our results reinforce GCH1 as a PD-relevant gene with clinical implications, whereas variants identified in other genes are rare and of uncertain relation to the PD phenotype. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keyword(s): Humans (MeSH) ; Parkinson Disease: genetics (MeSH) ; Parkinson Disease: complications (MeSH) ; Male (MeSH) ; Female (MeSH) ; Middle Aged (MeSH) ; Dystonia: genetics (MeSH) ; Aged (MeSH) ; GTP Cyclohydrolase: genetics (MeSH) ; Dystonic Disorders: genetics (MeSH) ; Adult (MeSH) ; Vesicular Transport Proteins: genetics (MeSH) ; GCH1 ; Parkinson's disease ; VPS16 ; dystonia ; monogenic ; GTP Cyclohydrolase ; GCH1 protein, human ; Vesicular Transport Proteins

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Contributing Institute(s):

1. Genome Biology of Neurodegenerative Diseases (AG Heutink)

Research Program(s):

1. 354 - Disease Prevention and Healthy Aging (POF4-354) (POF4-354)

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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