GIGYF2 in Parkinson's disease: Innocent until proven otherwise

Abstract

f o g o s d c i p e w c a f e c b u d c v o s We read with great interest the thoughtful follow-up study f GIGYF2 in French families with Parkinson’s disease (PD) y Lesage et al. (2009) reported in Neurobiology of Aging, nd welcome the opportunity to comment on their data as ell as the role of GIGY2 in PD genetic etiology in general. Two decades of molecular genetic research in PD has rovided us with 15 chromosomal loci, designated PARK1 o 15, associated with either autosomal dominant or recesive forms of this neurodegenerative disorder (Lesage and rice, 2009). Only at six of these PARK loci, pathogenic utations in genes have been unequivocally linked to PD (in pproximately 15% of PD patients), leaving the majority of enetic variability contributing to disease yet to be identified. ore recently, the PARK11 locus at chromosome 2q36-q37 egained interest of the field with the observation of a high requency of missense mutations in GIGYF2 in familial PD atients of European descent (Lautier et al., 2008). The majorty of independent follow-up studies, including ours, failed o detect proven pathogenic variants in or genetic associaion of GIGYF2 with sporadic and/or familial PD patients Bonetti et al., 2009; Bras et al., 2008; Di et al., 2009; Meeus t al., 2009; Nichols et al., 2009; Sutherland et al., 2009; ilarino-Guell et al., 2009; Zimprich et al., 2009). In total 6 different missense mutations were reported of which 21 ere observed only in PD patients, 9 only in control individals and 6 in both patients and control individuals (Fig. 1).