Parkinson's disease: from monogenic forms to genetic susceptibility factors
1 INSERM, UMR_S679, Paris, France 2 Université Pierre et Marie Curie-Paris6, UMR S679, Pitié-Salpêtrière, Paris, France 3 AP-HP, Groupe Pitié-Salpêtrière, Fédération des Maladies du Système Nerveux, Paris, France 4 AP-HP, Groupe Pitié-Salpêtrière, Département de Génétique, Cytogénétique et Embryologie, Paris, France
* To whom correspondence should be addressed. INSERM UMR_S679, Hôpital de la Salpêtrière, 47, Boulevard de l'Hôpital, 75651 Paris cedex 13, France. Tel: +33 142162182; Fax: +33 144243658; Email: alexis.brice{at}upmc.fr
Received December 23, 2008; Revised December 23, 2008; Accepted January 5, 2009
Research in Parkinson's disease (PD) genetics has been extremely prolific over the past decade. More than 13 loci and 9 genes have been identified, but their implication in PD is not always certain. Point mutations, duplications and triplications in the 
-synuclein (SNCA) gene cause a rare dominant form of PD in familial and sporadic cases. Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are a more frequent cause of autosomal dominant PD, particularly in certain ethnic groups. Loss-of-function mutations in Parkin, PINK1, DJ-1 and ATP13A2 cause autosomal recessive parkinsonism with early-onset. Identification of other Mendelian forms of PD will be a main challenge for the next decade. In addition, susceptibility variants that contribute to PD have been identified in several populations, such as polymorphisms in the SNCA, LRRK2 genes and heterozygous mutations in the β-glucocerebrosidase (GBA) gene. Genome-wide associations and re-sequencing projects, together with gene-environment interaction studies, are expected to further define the causal role of genetic determinants in the pathogenesis of PD, and improve prevention and treatment.
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