Genetic etiology of Parkinson disease associated with mutations in the SNCA, PARK2, PINK1, PARK7, and LRRK2 genes: a mutation update
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Open Access
- 18 May 2010
- journal article
- research article
- Published by Hindawi Limited in Human Mutation
- Vol. 31 (7), 763-780
- https://doi.org/10.1002/humu.21277
Abstract
To date, molecular genetic analyses have identified over 500 distinct DNA variants in five disease genes associated with familial Parkinson disease; α‐synuclein (SNCA), parkin (PARK2), PTEN‐induced putative kinase 1 (PINK1), DJ‐1 (PARK7), and Leucine‐rich repeat kinase 2 (LRRK2). These genetic variants include ∼82% simple mutations and ∼18% copy number variations. Some mutation subtypes are likely underestimated because only few studies reported extensive mutation analyses of all five genes, by both exonic sequencing and dosage analyses. Here we present an update of all mutations published to date in the literature, systematically organized in a novel mutation database (http://www.molgen.ua.ac.be/PDmutDB). In addition, we address the biological relevance of putative pathogenic mutations. This review emphasizes the need for comprehensive genetic screening of Parkinson patients followed by an insightful study of the functional relevance of observed genetic variants. Moreover, while capturing existing data from the literature it became apparent that several of the five Parkinson genes were also contributing to the genetic etiology of other Lewy Body Diseases and Parkinson‐plus syndromes, indicating that mutation screening is recommendable in these patient groups. Hum Mutat 31:763–780, 2010.This publication has 276 references indexed in Scilit:
- LRRK2 mutations and risk variants in Japanese patients with Parkinson's diseaseMovement Disorders, 2009
- Familial Parkinsonism and early onset Parkinson's disease in a Brazilian movement disorders clinic: Phenotypic characterization and frequency of SNCA, PRKN, PINK1, and LRRK2 mutationsMovement Disorders, 2009
- Risk of Parkinson Disease in Carriers of Parkin MutationsArchives of Neurology, 2008
- Case-Control Study of the Parkin Gene in Early-Onset Parkinson DiseaseArchives of Neurology, 2006
- DJ‐1 mutations and parkinsonism‐dementia‐amyotrophic lateral sclerosis complexAnnals of Neurology, 2005
- α-Synuclein produces a long-lasting increase in neurotransmitter releaseThe EMBO Journal, 2004
- α-synuclein locus duplication as a cause of familial Parkinson's diseaseThe Lancet, 2004
- The new mutation, E46K, of α‐synuclein causes parkinson and Lewy body dementiaAnnals of Neurology, 2003
- Mice Lacking α-Synuclein Display Functional Deficits in the Nigrostriatal Dopamine SystemNeuron, 2000
- AlaSOPro mutation in the gene encoding α-synuclein in Parkinson's diseaseNature Genetics, 1998