PRKN mutations have been linked to Parkinson’s disease (PD). Most of the mutational screenings have focused on the coding exons. The 3′ untranslated region (UTR) could also harbor functionally relevant nucleotide changes. We performed a mutational screening of PRKN in a cohort of early-onset PD patients (n=235) from Spain. We found 16 mutations (five new): 16 patients (7 %) carried two mutations and only one mutation was found in 28 (12 %). Patients with two mutations had significantly lower mean age (30±9 years) compared to patients with one (40±7) or no mutation (42±7). We found a total of 15 nucleotide variants (three new) in the 3′ UTR region. The frequency of carriers of the rare rs62637702 G allele (*94A/G) was significantly lower among the patients compared to healthy controls (n=418) (0.03 vs. 0.004; p<0.001), suggesting a protective role for this allele. In order to investigate the basal effect of this variant, we performed luciferase assays. No different basal activity was observed between the two associated with PD. This could be a surrogate marker for disease risk, in linkage disequilibrium with other nonidentified functional variant.
Reference: de Mena L, Samaranch L, Coto E, Cardo LF, Ribacoba R, Lorenzo-Betancor O, Pastor P, Wang L, Irigoyen J, Mata IF, Díaz M, Moris G, Menéndez M, Corao AI, Lorenzo E, Alvarez V. Mutational Screening of PARKIN Identified a 3' UTR Variant (rs62637702) Associated with Parkinson's Disease. J Mol Neurosci. 2012