Analysis of PArkin Co-Regulated Gene in a Taiwanese–Ethnic Chinese cohort with early-onset Parkinson's disease

PArkin Co-Regulated Gene (PACRG) is a novel gene which is transcriptionally co-regulated with the parkin gene (PRKN) by a shared bi-directional promoter. To determine whether mutations in PACRG are associated with early-onset Parkinson's disease (EO-PD), we performed sequence and dosage analysis of 76 EO-PD patients from a Taiwanese–Ethnic Chinese cohort. This analysis identified two novel nucleotide variants in the non-coding region of PACRG. One patient had an IVS2 + 247851T > C heterozygous change and two patients had an IVS4 + 78A > G heterozygous alteration. Neither of these variants was present in the 91 controls tested. A third intronic polymorphism (IVS1 + 85744insC) was present in cases and controls at an equivalent frequency (∼0.25). To facilitate gene dosage analysis, we identified cell lines with a heterozygous deletion or duplication of the entire PACRG locus. Three patients with heterozygous dosage alterations were identified, including two patients with an exon 2 duplication and one patient with an exon 3 deletion of PACRG. No dosage alterations were observed in the 91 controls analyzed (χ2 = 3.66, P = 0.056). Our results suggest that point mutations in PACRG are not a common cause of EO-PD but haploinsufficiency for PACRG may be associated with disease.