Exon rearrangements and point mutations are common in PARK2, the most important causative gene of autosomal recessive early-onset Parkinson disease (EOPD). However, gene dosage analysis alone cannot conclusively determine the phase of exon rearrangements and the incidence of molecularly confirmed parkin-type EOPD may be underestimated. To fully characterize the mutation spectrum, we performed sequencing and gene dosage analyses of SNCA, PARK2, PINK1, and PARK7 in 114 unrelated EOPD patients with onset age ≤40 years. Mutational phase of exon rearrangements was determined by reverse-transcriptase PCR (RT-PCR) and sequence analysis using a patient's own RNA. Fourteen different PARK2 mutations (3 point mutations plus 11 exon rearrangements) were identified in 18 patients, comprising 1 homozygote (0.9%), 13 compound heterozygotes (11.4%), 3 single heterozygotes (2.6%), and 1 with unknown phase (0.9%). By phase determination, more than 80% (5 of 6) of patients with apparently contiguous multi-exon deletions and 30% (5 of 18) of all PARK2 mutation carriers were additionally diagnosed as compound heterozygotes, respectively. This study shows that compound heterozygous mutations constituted a significant portion of patients with apparently contiguous multi-exon deletions. Phase determination is a prerequisite to molecular diagnosis for autosomal recessive EOPD, especially in subjects with PARK2 exon rearrangements.

Purpose Homozygous polymorphism of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene and resultant hyperhomocysteinaemia have been established as an independent risk factor for vascular diseases. There are evidences that vascular abnormalities are involved in the pathogenesis and progression of normaltension glaucoma (NTG). In the present study, we were to find out the associations between 677C4T and 1298A4C polymorphisms of the MTHFR gene and NTG. Methods This was a retrospective, casecontrolled study enrolling 78 NTG patients and 100 controls. DNA from peripheral blood lymphocytes was extracted and the genotypes of polymorphisms (677C4T and 1298A4C) in the MTHFR gene were determined using PCR followed by restriction enzyme digestion. The frequencies of the polymorphic genotypes in the patients with NTG and controls were compared. Results The frequencies of the polymorphisms of the MTHFR gene (677C4T and 1298A4C) in the NTG patients were not significantly different from those of controls. But the younger NTG patients (age at diagnosis p45 years) showed significantly higher prevalence of 677C4T polymorphism than the older NTG patients (age at diagnosis 445 years) (TT genotype, 38.9 vs 11.9%, P ¼ 0.006, OR ¼ 4.71, 95% CI ¼ 1.49-14.9) and than the younger control subgroup (TT genotype, 38.9 vs 6.1%, P ¼ 0.001, OR ¼ 9.86, 95% CI ¼ 2.23-42.4). Conclusions The 677C4T polymorphism was significantly associated with NTG in the younger patients, while 1298A4C polymorphism was not. This suggests that 677C4T polymorphism of the MTHFR gene can be a genetic risk factor of NTG in Korean population.