| Systematic Review and UK-Based Study of PARK2 (parkin), PINK1, PARK7 (DJ-1) and LRRK2 in early-onset Parkinson's disease. | |
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MedLine Citation:
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PMID: 22956510 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Laura L Kilarski; Justin P Pearson; Victoria Newsway; Elisa Majounie; M Duleeka W Knipe; Anjum Misbahuddin; Patrick F Chinnery; David J Burn; Carl E Clarke; Marie-Helene Marion; Alistair J Lewthwaite; David J Nicholl; Nicholas W Wood; Karen E Morrison; Caroline H Williams-Gray; Jonathan R Evans; Stephen J Sawcer; Roger A Barker; Mirdhu M Wickremaratchi; Yoav Ben-Shlomo; Nigel M Williams; Huw R Morris |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-9-6 |
Journal Detail:
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Title: Movement disorders : official journal of the Movement Disorder Society Volume: - ISSN: 1531-8257 ISO Abbreviation: Mov. Disord. Publication Date: 2012 Sep |
Date Detail:
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Created Date: 2012-9-7 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8610688 Medline TA: Mov Disord Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 Movement Disorder Society. |
Affiliation:
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MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Neurology, School of Medicine, Cardiff University, Cardiff, United Kingdom. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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