Parkin dosage mutations have greater pathogenicity in familial PD than simple sequence mutations.

ABSTRACT:

Objective

Mutations in both alleles of parkin have been shown to result in Parkinson disease (PD). However, it is unclear whether haploinsufficiency (presence of a mutation in only 1 of the 2 parkin alleles) increases the risk for PD.

Methods

We performed comprehensive dosage and sequence analysis of all 12 exons of parkin in a sample of 520 independent patients with familial PD and 263 controls. We evaluated whether presence of a single parkin mutation, either a sequence (point mutation or small insertion/deletion) or dosage (whole exon deletion or duplication) mutation, was found at increased frequency in cases as compared with controls. We then compared the clinical characteristics of cases with 0, 1, or 2 parkin mutations.

Results

We identified 55 independent pati

SUBMITTER: Pankratz N 

PROVIDER: S-EPMC2715211 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature