Document Detail

Systematic review and UK-based study of PARK2 (parkin), PINK1, PARK7 (DJ-1) and LRRK2 in early-onset Parkinson's disease.
MedLine Citation:
PMID:  22956510     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Review     Date:  2012-09-06
Journal Detail:
Title:  Movement disorders : official journal of the Movement Disorder Society     Volume:  27     ISSN:  1531-8257     ISO Abbreviation:  Mov. Disord.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-19     Completed Date:  2013-04-18     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  8610688     Medline TA:  Mov Disord     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1522-9     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Movement Disorder Society.
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MeSH Terms
Cohort Studies
DNA Mutational Analysis
Great Britain / epidemiology
Intracellular Signaling Peptides and Proteins / genetics*
Mutation / genetics*
Oncogene Proteins / genetics*
Parkinson Disease / epidemiology,  genetics*
Protein Kinases / genetics*
Protein-Serine-Threonine Kinases / genetics*
Ubiquitin-Protein Ligases / genetics*
Grant Support
G0700943//Medical Research Council; G0800784//Medical Research Council; G1100643//Medical Research Council
Reg. No./Substance:
0/Intracellular Signaling Peptides and Proteins; 0/Oncogene Proteins; 0/PARK7 protein, human; EC 2.7.-/Protein Kinases; EC protein, human; EC putative kinase; EC Kinases; EC Ligases; EC protein

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