Analysis of Parkin Co-Regulated Gene in a Taiwanese-Ethnic Chinese Cohort with Early-Onset Parkinson's Disease
Resource
PARKINSONISM & RELATED DISORDERS v.15 n.6 pp.417-421
Journal
PARKINSONISM & RELATED DISORDERS
Journal Volume
v.15
Journal Issue
n.6
Pages
417-421
Date Issued
2009
Date
2009
Author(s)
WU, RUEY-MEEI
Abstract
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 (approximately 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 (chi(2)=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.
Subjects
PACRG
Genetics
Early-onset Parkinson's disease
Mutation detection