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

• Published in: Movement disorders 2018-12, Vol.33 (12), p.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: Article
• Language: English
• Subjects: Dihydroxyphenylalanine; genetics; Genotypes; Hormone replacement therapy; Levodopa; LRRK2; LRRK2 protein; Movement disorders; Mutation; Neurodegenerative diseases; Parkinson's disease; Phenotypes; SNCA; Systematic review; VPS35
• ISSN: 0885-3185; 1531-8257
• DOI: 10.1002/mds.27527

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