PT  - JOURNAL ARTICLE
AU  - Hedrich, K.
AU  - Djarmati, A.
AU  - Schäfer, N.
AU  - Hering, R.
AU  - Wellenbrock, C.
AU  - Weiss, P. H.
AU  - Hilker, R.
AU  - Vieregge, P.
AU  - Ozelius, L. J.
AU  - Heutink, P.
AU  - Bonifati, V.
AU  - Schwinger, E.
AU  - Lang, A. E.
AU  - Noth, J.
AU  - Bressman, S. B.
AU  - Pramstaller, P. P.
AU  - Riess, O.
AU  - Klein, C.
TI  - <em>DJ-1 (PARK7)</em> mutations are less frequent than <em>Parkin (PARK2)</em> mutations in early-onset Parkinson disease
AID  - 10.1212/01.WNL.0000113022.51739.88
DP  - 2004 Feb 10
TA  - Neurology
PG  - 389--394
VI  - 62
IP  - 3
4099  - http://n.neurology.org/content/62/3/389.short
4100  - http://n.neurology.org/content/62/3/389.full
SO  - Neurology2004 Feb 10; 62
AB  - Background: Mutations in the Parkin gene (PARK2) are the most commonly identified cause of recessively inherited early-onset Parkinson disease (EOPD) but account for only a portion of cases. DJ-1 (PARK7) 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. Methods: To investigate the frequency of DJ-1 mutations, the authors performed mutational analysis of all six coding exons of DJ-1 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, Parkin analysis was performed as previously described. Results: The authors identified two carriers of single heterozygous loss-of-function DJ-1 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 DJ-1 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 Parkin gene. Conclusions: Mutations in DJ-1 are less frequent than mutations in Parkin in EOPD patients but should be considered as a possible cause of EOPD. The effect of single heterozygous mutations in DJ-1 on the nigrostriatal system, as described for heterozygous changes in Parkin and PARK6, remains to be elucidated.