Early-onset parkinsonism associated with PINK1 mutations: Frequency, genotypes, and phenotypes

摘要

We read with great interest the recent report by Bonifati et al. demonstrating that the transcript of an allele bearing the c.1366C>T (Gln456Stop) mutation in the PINK1 gene associated with early-onset Parkinson disease (PD) is not detectable by PCR in two unrelated families.The authors explained this finding by either lack of expression of the mutant allele or by instability due to the mutation or another change in linkage disequilibrium with the c.1366T alteration. They conclude that this variant is an example of a mutant allele that exerts its major pathogenic effect in PD at the mRNA rather than at the protein level.We identified a large German PD family with four affected siblings who were all homozygous for the c.1366C>T mutation. We also studied 11 of their asymptomatic heterozygous children and 5 mutation-negative family members. To address the question of an effect of this mutation on the mRNA level, we collected fresh blood from all 20 family members and extracted RNA that was reverse transcribed.