DJ-1 (PARK7) mutations are less frequent than Parkin (PARK2) mutations in early-onset Parkinson disease.

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.

The quantitative relationship of urinary peptide hydroxyproline excretion to collagen degradation.

To determine the quantitative relationship of urinary hydroxyproline peptide excretion to collagen breakdown, known quantities of radioactive hydroxyproline peptides were administered to unlabeled animals and excertion of radioactivity in respiratory carbon dioxide, urine, and feces was measured. The major routes of excretion of collagen peptide metabolites were respiratory carbon dioxide (75%) and urine, as hydroxyproline-containing peptides (25%). Since the predominant urine hydroxyproline peptide linkage is proly-hydroxyproline, L-prolyl-L-hydroxyproline-(3)H was administered to unlabeled animals. Greater than 80% of the administered dipeptide was excreted in urine, suggesting that this peptide linkage is not hydrolyzed to a significant extent in vivo. These data suggest that urinary hydroxyproline excretion is a "fairly" sensitive indicator of collagen breakdown and can be used at the clinical level to quantitate changes in collagen breakdown.