Funding agencies: This work was supported by the Medical Research Council UK (G0700943), Parkinson's UK (Grant 8047), the Cambridge NIHR Biomedical Research Centre, the Midlands Neuroscience Teaching and Research Fund, the Sandwell and West Birmingham Hospitals NHS Trust, the Ipsen Fund, the Wellcome Trust, and a Patrick Berthoud Clinical Research Fellowship and Raymond and Beverly Sackler studentship.
Article first published online: 6 SEP 2012
Copyright © 2012 Movement Disorder Society
Volume 27, Issue 12, pages 1522–1529, October 2012
How to Cite
Kilarski, L. L., Pearson, J. P., Newsway, V., Majounie, E., Knipe, M. D. W., Misbahuddin, A., Chinnery, P. F., Burn, D. J., Clarke, C. E., Marion, M.-H., Lewthwaite, A. J., Nicholl, D. J., Wood, N. W., Morrison, K. E., Williams-Gray, C. H., Evans, J. R., Sawcer, S. J., Barker, R. A., Wickremaratchi, M. M., Ben-Shlomo, Y., Williams, N. M. and Morris, H. R. (2012), Systematic Review and UK-Based Study of PARK2 (parkin), PINK1, PARK7 (DJ-1) and LRRK2 in early-onset Parkinson's disease. Mov. Disord., 27: 1522–1529. doi: 10.1002/mds.25132
Relevant conflicts of interest/financial disclosures: Nothing to report.
Full financial disclosures and author roles may be found in the online version of this article.
- Issue published online: 18 OCT 2012
- Article first published online: 6 SEP 2012
- Manuscript Accepted: 12 JUL 2012
- Manuscript Revised: 26 JUN 2012
- Manuscript Received: 27 OCT 2011
- systematic review;
- early-onset Parkinson's disease;
- parkin, DJ-1
Approximately 3.6% of patients with Parkinson's disease develop symptoms before age 45. Early-onset Parkinson's disease (EOPD) patients have a higher familial recurrence risk than late-onset patients, and 3 main recessive EOPD genes have been described. We aimed to establish the prevalence of mutations in these genes in a UK cohort and in previous studies. We screened 136 EOPD probands from a high-ascertainment regional and community-based prevalence study for pathogenic mutations in PARK2 (parkin), PINK1, PARK7 (DJ-1), and exon 41 of LRRK2. We also carried out a systematic review, calculating the proportion of cases with pathogenic mutations in previously reported studies. We identified 5 patients with pathogenic PARK2, 1 patient with PINK1, and 1 with LRRK2 mutations. The rate of mutations overall was 5.1%. Mutations were more common in patients with age at onset (AAO) < 40 (9.5%), an affected first-degree relative (6.9%), an affected sibling (28.6%), or parental consanguinity (50%). In our study EOPD mutation carriers were more likely to present with rigidity and dystonia, and 6 of 7 mutation carriers had lower limb symptoms at onset. Our systematic review included information from >5800 unique cases. Overall, the weighted mean proportion of cases with PARK2 (parkin), PINK1, and PARK7 (DJ-1) mutations was 8.6%, 3.7%, and 0.4%, respectively. PINK1 mutations were more common in Asian subjects. The overall frequency of mutations in known EOPD genes was lower than previously estimated. Our study shows an increased likelihood of mutations in patients with lower AAO, family history, or parental consanguinity. © 2012 Movement Disorder Society.