Systematic Review and UK-Based Study of PARK2 (parkin), PINK1, PARK7 (DJ-1) and LRRK2 in early-onset Parkinson's disease

被引：131

作者：

Kilarski, Laura L. ^{[1
]}

Pearson, Justin P. ^{[1
]}

Newsway, Victoria ^{[1
]}

Majounie, Elisa ^{[1
]}

Knipe, M. Duleeka W.

Misbahuddin, Anjum

Chinnery, Patrick F. ^{[2
]}

Burn, David J. ^{[2
,8
]}

Clarke, Carl E. ^{[3
,4
]}

Marion, Marie-Helene ^{[5
]}

Lewthwaite, Alistair J. ^{[3
,6
,7
]}

Nicholl, David J. ^{[3
,4
]}

Wood, Nicholas W. ^{[7
]}

Morrison, Karen E. ^{[3
,6
]}

Williams-Gray, Caroline H. ^{[9
]}

Evans, Jonathan R. ^{[9
]}

Sawcer, Stephen J. ^{[9
]}

Barker, Roger A. ^{[9
]}

Wickremaratchi, Mirdhu M. ^{[10
]}

Ben-Shlomo, Yoav ^{[11
]}

Williams, Nigel M. ^{[1
]}

Morris, Huw R. ^{[1
]}

机构：

[1] Cardiff Univ, Sch Med, Dept Neurol, MRC Ctr Neuropsychiat Genet & Genom, Cardiff, S Glam, Wales

[2] Newcastle Univ, Inst Med Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England

[3] Univ Birmingham, Coll Med & Dent Sci, Sch Clin & Expt Med, Birmingham, W Midlands, England

[4] Sandwell & W Birmingham Hosp NHS Trust, Birmingham, W Midlands, England

[5] St George Hosp, Dept Neurol, London, England

[6] Univ Hosp Birmingham NHS Trust, Birmingham, W Midlands, England

[7] UCL, Inst Neurol, Dept Mol Neurosci, London, England

[8] City Hosp, Birmingham, W Midlands, England

[9] Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Cambridge CB2 2QQ, England

[10] Worthing Dist Hosp, Dept Neurol, Worthing, England

[11] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England

来源：

MOVEMENT DISORDERS | 2012年 / 27卷 / 12期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

systematic review; PARK2; PINK1; PARK7; LRRK2; early-onset Parkinson's disease; parkin; DJ-1; AUTOSOMAL RECESSIVE PARKINSONISM; MITOCHONDRIAL DYSFUNCTION; JUVENILE PARKINSONISM; FAMILIAL AGGREGATION; MUTATIONS; GENE; FEATURES; DROSOPHILA-PINK1; METAANALYSIS; ASSOCIATION;

D O I：

10.1002/mds.25132

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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. (c) 2012 Movement Disorder Society.

引用

页码：1522 / 1529

页数：8

共 39 条

[1] A wide variety of mutations in the parkin gene are responsible for autosomal recessive parkinsonism in Europe [J].