Parkinson's disease (PD) is a neurodegenerative disorder in which relatives of the probands are affected approximately 4 times as frequently as relatives of control subjects. Several genes have been implicated as genetic risk factors for PD. We investigated the presence of six reported genetic variations in the SCNA , NR4A2 , and DJ ‐ 1 genes in 292 cases of familial Parkinson's disease from the Gene PD study. None of the variants were found in the Gene PD families. Our results suggest that other variants or genes account for the familial risk of PD within the Gene PD study. © 2005 Movement Disorder Society

The effects of a self-supervised home exercise program and a physiotherapist-supervised exercise program on motor symptoms in Parkinson's disease (PD) patients were compared in a prospective single-blinded clinical trial. Nineteen subjects (6 women, 13 men; mean age, 65 +/- 8 years) with Hoehn and Yahr Stages 2 to 3 were recruited. Subjects were self-selected into an 8-week exercise program that was self-supervised (HOME group) or physiotherapist-supervised (PT group). The primary outcome measurement was the Unified Parkinson's Disease Rating Scale (UPDRS) Motor subsection score (UPDRSm). The secondary outcome measurements were the Berg Balance Scale, Timed Up and Go Test, UPDRS Total score, and the Activities-specific Balance Confidence Scale. All outcomes were assessed at baseline and at 8 and 16 weeks after the start of the study. The investigators were blinded to the subject treatment group. Bonferroni-corrected paired Student's t test was used to evaluate the change in the UPDRSm from baseline to 8 weeks. Ninety-five percent confidence intervals (0) were calculated for the change in the secondary outcome measurements from baseline to 8 weeks. There was statistically significant and equal decrease in the UPDRSm from baseline to 8 weeks in both treatment groups. There was no difference in the 95% CI in the change of the secondary outcome measurements. A self-supervised exercise program was found to have similar effectiveness as a physiotherapist-supervised exercise program in improving motor symptoms in PD patients. This finding is important in the counseling of PD patients regarding adjunctive treatment of motor symptoms of PD with exercise. (c) 2005 Movement Disorder Society.

OBJECTIVE:To identify a haplotype influencing onset age for Parkinson's disease (PD) in the PARK3 region on chromosome 2p13.METHODS:Single nucleotide polymorphisms (SNP) spanning 2.2 Mb and located in or near potential candidate genes were used to fine map the PARK3 region in 527 patients with familial PD, from 264 families.RESULTS:TT homozygotes for rs1876487 (G/T) had a 7.4-year younger mean age at onset (p = 0.005) compared to patients with GT and GG genotypes. Furthermore, SNP flanking the sepiapterin reductase (7,8-dihydrobiopterin: NADP+ oxidoreductase) (SPR) gene, rs1876487 (p = 0.02) and rs1150500 (p = 0.04), were associated with younger onset age among persons who did not carry the 174 allele of D2S1394. The SPR gene is implicated in dopamine synthesis. Haplotype analysis of three SNP-rs2421095, rs1876487, rs1561244-revealed an association with onset age (p = 0.023) and a haplotype of A-T-G alleles was associated with younger onset for PD (p = 0.005).CONCLUSIONS:A haplotype at the PARK3 locus, harboring the SPR gene, is associated with onset age of PD. This may suggest a role for the SPR gene in modifying the age at onset of PD.

Parkinson disease (PD) is a late-onset neurodegenerative disorder. The mean age at onset is 61 years, but the disease can range from juvenile cases to cases in the 8th or 9th decade of life. The parkin gene on chromosome 6q and loci on chromosome 1p35-36 and 1p36 are responsible for some cases of autosomal recessive early-onset parkinsonism, but they do not appear to influence susceptibility or variability of age at onset for idiopathic PD. We have performed a genomewide linkage analysis using variance-component methodology to identify genes influencing age at onset of PD in a population of affected relatives (mainly affected sibling pairs) participating in the GenePD study. Four chromosomal loci showed suggestive evidence of linkage: chromosome 2p (maximum multipoint LOD [MaxLOD] = 2.08), chromosome 9q (MaxLOD = 2.00), chromosome 20 (MaxLOD = 1.82), and chromosome 21 (MaxLOD = 2.21). The 2p and 9q locations that we report here have previously been reported as loci influencing PD affection status. Association between PD age at onset and allele 174 of marker D2S1394, located on 2p13, was observed in the GenePD sample (P=.02). This 174 allele is common to the PD haplotype observed in two families that show linkage to PARK3 and have autosomal dominant PD, which suggests that this allele may be in linkage disequilibrium with a mutation influencing PD susceptibility or age at onset of PD.

OBJECTIVE:To examine patterns of familial aggregation and factors influencing onset age in a sample of siblings with PD.METHODS:Sibling pairs (n = 203) with PD were collected as part of the GenePD study. Standardized family history, medical history, and risk factor data were collected and analyzed.RESULTS:The mean age at onset was 61.4 years and did not differ according to sex, exposure to coffee, alcohol, or pesticides. Head trauma was associated with younger onset (p = 0.03) and multivitamin use with later onset (p = 0.007). Age at onset correlation between sibling pairs was significant (r = 0.56, p = 0.001) and was larger than the correlation in year of onset (r = 0.29). The mean difference in onset age between siblings was 8.7 years (range, 0 to 30 years). Female sex was associated with increased frequency of relatives with PD. The frequency of affected parents (7.0%) and siblings (5.1%) was increased when compared with frequency in spouses (2.0%).CONCLUSIONS:The greater similarity for age at onset than for year of onset in sibling pairs with PD, together with increased risk for biological relatives over spouses of cases, supports a genetic component for PD. Risk to siblings in this series is increased over that seen in random series of PD cases; however, patients in this sample have similar ages at onset and sex distribution as seen for PD generally. These analyses suggest that factors influencing penetrance are critical to the understanding of this disease.

A genome-wide scan for idiopathic PD in a sample of 113 PD-affected sibling pairs is reported. Suggestive evidence for linkage was found for chromosomes 1 (214 cM, lod = 1.20), 9 (136 cM, lod = 1.30), 10 (88 cM, lod = 1.07), and 16 (114 cM, lod = 0.93). The chromosome 9 region overlaps the genes for dopamine beta-hydroxylase and torsion dystonia. Although no strong evidence for linkage was found for any locus, these results may be of value in comparison with similar studies by others.