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 (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.
Taylor
Juliet M
JM
Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Victoria, Australia.
Wu
Ruey-Meei
RM
Farrer
Matthew J
MJ
Delatycki
Martin B
MB
Lockhart
Paul J
PJ
D000328:Adult; D044466:Asian People / Q000235:genetics; D002874:Chromosome Mapping; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008840:Microfilament Proteins; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics*; D013624:Taiwan / Q000208:ethnology
D008840:Microfilament Proteins; D018832:Molecular Chaperones; C471711:PACRG protein, human