Genetic etiology of Parkinson disease associated with mutations in the SNCA, PARK2, PINK1, PARK7 and LRRK2 genes: a mutation update

Karen Nuytemans (1, 2) , Jessie Theuns (1, 2) , Marc Cruts (1, 2) , Christine van Broeckhoven (1, 2)

1 Neurodegenerative Brain Diseases Group, Department of Molecular Genetics
2 Laboratory of Neurogenetics, Institute Born-Bunge

To date, molecular genetic analyses have identified over 500 distinct DNA variants in five disease genes associated with familial Parkinson disease; -synuclein (SNCA), parkin (PARK2), PTEN-induced putative kinase 1 (PINK1), DJ-1 (PARK7), Leucine-rich repeat kinase 2 (LRRK2). These genetic variants include ~82% simple mutations and ~18% copy number variations. Some mutation subtypes are likely underestimated since only few studies reported extensive mutation analyses of all five genes, by both exonic sequencing and dosage analyses. Here we present a mutation update of all reported mutations 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.

Mots clés: Life Sciences

Karen Nuytemans, Jessie Theuns, Marc Cruts, Christine van Broeckhoven. Genetic etiology of Parkinson disease associated with mutations in the SNCA, PARK2, PINK1, PARK7 and LRRK2 genes: a mutation update. Human Mutation, 2010, 31 (7), pp.763. ⟨10.1002/humu.21277⟩. ⟨hal-00552395⟩