Genotype‐phenotype relations for the Parkinson's disease genes SNCA, LRRK2, VPS35: MDSGene systematic review

Genotype‐phenotype relations for the Parkinson's disease genes SNCA, LRRK2, VPS35: MDSGene systematic review

ABSTRACT This comprehensive MDSGene review is devoted to the three autosomal‐dominant PD forms: PARK‐SNCA, PARK‐LRRK2, and PARK‐VPS35. It follows MDSGene's standardized data extraction protocol, screened a total of 2,972 citations, and is based on fully curated phenotypic and genotypic data on...

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Published in:Movement disorders Vol. 33; no. 12; pp. 1857 - 1870
Main Authors: Trinh, Joanne, Zeldenrust, Florentine M.J., Huang, Jana, Kasten, Meike, Schaake, Susen, Petkovic, Sonja, Madoev, Harutyun, Grünewald, Anne, Almuammar, Shahad, König, Inke R., Lill, Christina M., Lohmann, Katja, Klein, Christine, Marras, Connie
Format: Journal Article
Language:English
Published: United States Wiley Subscription Services, Inc 01-12-2018
Subjects:
Dihydroxyphenylalanine
genetics
Genotypes
Hormone replacement therapy
Levodopa
LRRK2
LRRK2 protein
Movement disorders
Mutation
Neurodegenerative diseases
Parkinson's disease
Phenotypes
SNCA
Systematic review
VPS35
VPS35
Parkinson's disease
genetics
LRRK2
SNCA
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Summary:ABSTRACT This comprehensive MDSGene review is devoted to the three autosomal‐dominant PD forms: PARK‐SNCA, PARK‐LRRK2, and PARK‐VPS35. It follows MDSGene's standardized data extraction protocol, screened a total of 2,972 citations, and is based on fully curated phenotypic and genotypic data on 937 patients with dominantly inherited PD attributed to 44 different mutations in SNCA, LRRK2, or VPS35. All of these data are also available in an easily searchable online database (www.mdsgene.org), which additionally provides descriptive summary statistics on phenotypic and genetic data. Despite the high degree of missingness of phenotypic features and unsystematic reporting of genotype data in the original literature, the present review recapitulates many of the previously described findings including later onset of disease (median age at onset: ∼49 years) compared to recessive forms of PD of an overall excellent treatment response. Our systematic review validates previous reports showing that SNCA mutation carriers have a younger age at onset compared to LRRK2 and VPS35 (P < 0.001). SNCA mutation carriers often have additional psychiatric symptoms, and although not exclusive to only LRRK2 or VPS35 mutation carriers, LRRK2 mutation carriers have a typical form of PD, and, lastly, VPS35 mutation carriers have good response to l‐dopa. © 2018 International Parkinson and Movement Disorder Society
Bibliography:Full financial disclosures and author roles may be found in the online version of this article.
Joanne Trinh, Florentine M.J. Zeldenrust, Jana Huang, and Meike Kasten contributed equally to this work.
Nothing to report.
Relevant conflicts of interest/financial disclosures
Funding agencies
The study was supported by the International Parkinson and Movement Disorder Society (to C.K., C.M.), by the Deutsche Forschungsgemeinschaft (FOR2488) to C.K., M.K., A.G., K.L., C.M.L., and I.R.K. and by intramural funds from the University of Lübeck (to C.K.). C.K. is the recipient of a career development award from the Hermann and Lilly Schilling Foundation. J.T. is the recipient of a postdoctoral fellowship from the Alexander Von Humboldt Foundation, Canadian Institutes of Health Research, and Joachim Herz Stiftung Fellowship. A.G. is the recipient of an ATTRACT career development grant from the Luxembourg Research Fund (FNR).
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ISSN:0885-3185
1531-8257
DOI:10.1002/mds.27527