<i>DJ-1 (PARK7)</i> mutations are less frequent than <i>Parkin (PARK2)</i> mutations in early-onset Parkinson disease

Abstract

<b><i>Background:</i></b> Mutations in the <i>Parkin</i> gene (<i>PARK2</i>) are the most commonly identified cause of recessively inherited early-onset Parkinson disease (EOPD) but account for only a portion of cases. <i>DJ-1</i> (<i>PARK7</i>) was recently reported as a second gene associated with recessively inherited PD with a homozygous exon deletion and a homozygous point mutation in two families. <b><i>Methods:</i></b> To investigate the frequency of <i>DJ-1</i> mutations, the authors performed mutational analysis of all six coding exons of <i>DJ-1</i> in 100 EOPD patients. For the detection of exon rearrangements, the authors developed a quantitative duplex PCR assay. Denaturing high performance liquid chromatography analysis was used to screen for point mutations and small deletions. Further, <i>Parkin</i> analysis was performed as previously described. <b><i>Results:</i></b> The authors identified two carriers of single heterozygous loss-of-function <i>DJ-1</i> mutations, including a heterozygous deletion of exons 5 to 7 and an 11-base pair deletion, removing the invariant donor splice site in intron 5. Interestingly, both <i>DJ-1</i> mutations identified in this study were found in the heterozygous state only. The authors also detected a polymorphism (R98Q) in 1.5% of the chromosomes in both the patient and control group. In the same patient sample, 17 cases were detected with mutations in the <i>Parkin</i> gene. <b><i>Conclusions:</i></b> Mutations in <i>DJ-1</i> are less frequent than mutations in <i>Parkin</i> in EOPD patients but should be considered as a possible cause of EOPD. The effect of single heterozygous mutations in <i>DJ-1</i> on the nigrostriatal system, as described for heterozygous changes in <i>Parkin</i> and <i>PARK6</i>, remains to be elucidated.