Systematic Review and UK-Based Study of PARK2 (parkin), PINK1, PARK7 (DJ-1) and LRRK2 in Early-Onset Parkinson's Disease
Identifieur interne : 000054 ( PascalFrancis/Corpus ); précédent : 000053; suivant : 000055Systematic Review and UK-Based Study of PARK2 (parkin), PINK1, PARK7 (DJ-1) and LRRK2 in Early-Onset Parkinson's Disease
Auteurs : 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. MorrisSource :
- Movement disorders [ 0885-3185 ] ; 2012.
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Abstract
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), PINK 1, 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.
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| NO : | PASCAL 12-0423953 INIST |
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| ET : | Systematic Review and UK-Based Study of PARK2 (parkin), PINK1, PARK7 (DJ-1) and LRRK2 in Early-Onset Parkinson's Disease |
| AU : | KILARSKI (Laura L.); PEARSON (Justin P.); NEWSWAY (Victoria); MAJOUNIE (Elisa); KNIPE (M. Duleeka W.); MISBAHUDDIN (Anjum); CHINNERY (Patrick F.); BURN (David J.); CLARKE (Carl E.); MARION (Marie-Helene); LEWTHWAITE (Alistair J.); NICHOLL (David J.); WOOD (Nicholas W.); MORRISON (Karen E.); WILLIAMS-GRAY (Caroline H.); EVANS (Jonathan R.); SAWCER (Stephen J.); BARKER (Roger A.); WICKREMARATCHI (Mirdhu M.); BEN-SHLOMO (Yoav); WILLIAMS (Nigel M.); MORRIS (Huw R.) |
| AF : | MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Neurology, School of Medicine, Cardiff University/Cardiff/Royaume-Uni (1 aut., 2 aut., 3 aut., 4 aut., 21 aut., 22 aut.); Department of Neurology, School of Medicine, Cardiff University/Cardiff/Royaume-Uni (5 aut.); Department of Neurology, Barking, Havering & Redbridge University Hospitals NHS Trust/Royaume-Uni (6 aut.); Institute of Genetic Medicine, Newcastle University, Central Parkway/Newcastle upon Tyne/Royaume-Uni (7 aut., 8 aut.); School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham/Birmingham/Royaume-Uni (9 aut., 11 aut., 12 aut., 14 aut.); Sandwell and West Birmingham Hospitals NHS Trust/Royaume-Uni (9 aut., 12 aut.); Department of Neurology, St George's Hospital/London/Royaume-Uni (10 aut.); University Hospitals Birmingham NHS Trust/Birmingham/Royaume-Uni (11 aut., 14 aut.); Department of Molecular Neuroscience, Institute of Neurology, University College London/London/Royaume-Uni (11 aut., 13 aut.); City Hospital/Birmingham/Royaume-Uni (12 aut.); Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's, Hospital, Hills Road/Cambridge/Royaume-Uni (15 aut., 16 aut., 17 aut., 18 aut.); Department of Neurology, Worthing Hospital/Worthing/Royaume-Uni (19 aut.); School of Social and Community Medicine, Bristol University/Bristol/Royaume-Uni (20 aut.) |
| DT : | Publication en série; Niveau analytique |
| SO : | Movement disorders; ISSN 0885-3185; Etats-Unis; Da. 2012; Vol. 27; No. 12; Pp. 1522-1529; Bibl. 39 ref. |
| LA : | Anglais |
| EA : | 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), PINK 1, 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. |
| CC : | 002B17; 002B17G |
| FD : | Maladie de Parkinson; Pathologie du système nerveux; Parkine |
| FG : | Pathologie de l'encéphale; Syndrome extrapyramidal; Maladie dégénérative; Pathologie du système nerveux central |
| ED : | Parkinson disease; Nervous system diseases; Parkin |
| EG : | Cerebral disorder; Extrapyramidal syndrome; Degenerative disease; Central nervous system disease |
| SD : | Parkinson enfermedad; Sistema nervioso patología; Parkin |
| LO : | INIST-20953.354000502081650100 |
| ID : | 12-0423953 |
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Lewthwaite</name><affiliation><inist:fA14 i1="05"><s1>School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham</s1><s2>Birmingham</s2><s3>GBR</s3><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="08"><s1>University Hospitals Birmingham NHS Trust</s1><s2>Birmingham</s2><s3>GBR</s3><sZ>11 aut.</sZ><sZ>14 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="09"><s1>Department of Molecular Neuroscience, Institute of Neurology, University College London</s1><s2>London</s2><s3>GBR</s3><sZ>11 aut.</sZ><sZ>13 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Nicholl, David J" sort="Nicholl, David J" uniqKey="Nicholl D" first="David J." last="Nicholl">David J. Nicholl</name><affiliation><inist:fA14 i1="05"><s1>School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham</s1><s2>Birmingham</s2><s3>GBR</s3><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="06"><s1>Sandwell and West Birmingham Hospitals NHS Trust</s1><s3>GBR</s3><sZ>9 aut.</sZ><sZ>12 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="10"><s1>City Hospital</s1><s2>Birmingham</s2><s3>GBR</s3><sZ>12 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Wood, Nicholas W" sort="Wood, Nicholas W" uniqKey="Wood N" first="Nicholas W." last="Wood">Nicholas W. Wood</name><affiliation><inist:fA14 i1="09"><s1>Department of Molecular Neuroscience, Institute of Neurology, University College London</s1><s2>London</s2><s3>GBR</s3><sZ>11 aut.</sZ><sZ>13 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Morrison, Karen E" sort="Morrison, Karen E" uniqKey="Morrison K" first="Karen E." last="Morrison">Karen E. Morrison</name><affiliation><inist:fA14 i1="05"><s1>School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham</s1><s2>Birmingham</s2><s3>GBR</s3><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="08"><s1>University Hospitals Birmingham NHS Trust</s1><s2>Birmingham</s2><s3>GBR</s3><sZ>11 aut.</sZ><sZ>14 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Williams Gray, Caroline H" sort="Williams Gray, Caroline H" uniqKey="Williams Gray C" first="Caroline H." last="Williams-Gray">Caroline H. Williams-Gray</name><affiliation><inist:fA14 i1="11"><s1>Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's, Hospital, Hills Road</s1><s2>Cambridge</s2><s3>GBR</s3><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Evans, Jonathan R" sort="Evans, Jonathan R" uniqKey="Evans J" first="Jonathan R." last="Evans">Jonathan R. Evans</name><affiliation><inist:fA14 i1="11"><s1>Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's, Hospital, Hills Road</s1><s2>Cambridge</s2><s3>GBR</s3><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Sawcer, Stephen J" sort="Sawcer, Stephen J" uniqKey="Sawcer S" first="Stephen J." last="Sawcer">Stephen J. Sawcer</name><affiliation><inist:fA14 i1="11"><s1>Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's, Hospital, Hills Road</s1><s2>Cambridge</s2><s3>GBR</s3><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Barker, Roger A" sort="Barker, Roger A" uniqKey="Barker R" first="Roger A." last="Barker">Roger A. Barker</name><affiliation><inist:fA14 i1="11"><s1>Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's, Hospital, Hills Road</s1><s2>Cambridge</s2><s3>GBR</s3><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Wickremaratchi, Mirdhu M" sort="Wickremaratchi, Mirdhu M" uniqKey="Wickremaratchi M" first="Mirdhu M." last="Wickremaratchi">Mirdhu M. Wickremaratchi</name><affiliation><inist:fA14 i1="12"><s1>Department of Neurology, Worthing Hospital</s1><s2>Worthing</s2><s3>GBR</s3><sZ>19 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Ben Shlomo, Yoav" sort="Ben Shlomo, Yoav" uniqKey="Ben Shlomo Y" first="Yoav" last="Ben-Shlomo">Yoav Ben-Shlomo</name><affiliation><inist:fA14 i1="13"><s1>School of Social and Community Medicine, Bristol University</s1><s2>Bristol</s2><s3>GBR</s3><sZ>20 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Williams, Nigel M" sort="Williams, Nigel M" uniqKey="Williams N" first="Nigel M." last="Williams">Nigel M. Williams</name><affiliation><inist:fA14 i1="01"><s1>MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Neurology, School of Medicine, Cardiff University</s1><s2>Cardiff</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>21 aut.</sZ><sZ>22 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Morris, Huw R" sort="Morris, Huw R" uniqKey="Morris H" first="Huw R." last="Morris">Huw R. Morris</name><affiliation><inist:fA14 i1="01"><s1>MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Neurology, School of Medicine, Cardiff University</s1><s2>Cardiff</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>21 aut.</sZ><sZ>22 aut.</sZ></inist:fA14></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">12-0423953</idno><date when="2012">2012</date><idno type="stanalyst">PASCAL 12-0423953 INIST</idno><idno type="RBID">Pascal:12-0423953</idno><idno type="wicri:Area/PascalFrancis/Corpus">000054</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Systematic Review and UK-Based Study of PARK2 (parkin), PINK1, PARK7 (DJ-1) and LRRK2 in Early-Onset Parkinson's Disease</title><author><name sortKey="Kilarski, Laura L" sort="Kilarski, Laura L" uniqKey="Kilarski L" first="Laura L." last="Kilarski">Laura L. Kilarski</name><affiliation><inist:fA14 i1="01"><s1>MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Neurology, School of Medicine, Cardiff University</s1><s2>Cardiff</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>21 aut.</sZ><sZ>22 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Pearson, Justin P" sort="Pearson, Justin P" uniqKey="Pearson J" first="Justin P." last="Pearson">Justin P. Pearson</name><affiliation><inist:fA14 i1="01"><s1>MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Neurology, School of Medicine, Cardiff University</s1><s2>Cardiff</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>21 aut.</sZ><sZ>22 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Newsway, Victoria" sort="Newsway, Victoria" uniqKey="Newsway V" first="Victoria" last="Newsway">Victoria Newsway</name><affiliation><inist:fA14 i1="01"><s1>MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Neurology, School of Medicine, Cardiff University</s1><s2>Cardiff</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>21 aut.</sZ><sZ>22 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Majounie, Elisa" sort="Majounie, Elisa" uniqKey="Majounie E" first="Elisa" last="Majounie">Elisa Majounie</name><affiliation><inist:fA14 i1="01"><s1>MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Neurology, School of Medicine, Cardiff University</s1><s2>Cardiff</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>21 aut.</sZ><sZ>22 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Knipe, M Duleeka W" sort="Knipe, M Duleeka W" uniqKey="Knipe M" first="M. Duleeka W." last="Knipe">M. Duleeka W. Knipe</name><affiliation><inist:fA14 i1="02"><s1>Department of Neurology, School of Medicine, Cardiff University</s1><s2>Cardiff</s2><s3>GBR</s3><sZ>5 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Misbahuddin, Anjum" sort="Misbahuddin, Anjum" uniqKey="Misbahuddin A" first="Anjum" last="Misbahuddin">Anjum Misbahuddin</name><affiliation><inist:fA14 i1="03"><s1>Department of Neurology, Barking, Havering & Redbridge University Hospitals NHS Trust</s1><s3>GBR</s3><sZ>6 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Chinnery, Patrick F" sort="Chinnery, Patrick F" uniqKey="Chinnery P" first="Patrick F." last="Chinnery">Patrick F. Chinnery</name><affiliation><inist:fA14 i1="04"><s1>Institute of Genetic Medicine, Newcastle University, Central Parkway</s1><s2>Newcastle upon Tyne</s2><s3>GBR</s3><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Burn, David J" sort="Burn, David J" uniqKey="Burn D" first="David J." last="Burn">David J. Burn</name><affiliation><inist:fA14 i1="04"><s1>Institute of Genetic Medicine, Newcastle University, Central Parkway</s1><s2>Newcastle upon Tyne</s2><s3>GBR</s3><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Clarke, Carl E" sort="Clarke, Carl E" uniqKey="Clarke C" first="Carl E." last="Clarke">Carl E. Clarke</name><affiliation><inist:fA14 i1="05"><s1>School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham</s1><s2>Birmingham</s2><s3>GBR</s3><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="06"><s1>Sandwell and West Birmingham Hospitals NHS Trust</s1><s3>GBR</s3><sZ>9 aut.</sZ><sZ>12 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Marion, Marie Helene" sort="Marion, Marie Helene" uniqKey="Marion M" first="Marie-Helene" last="Marion">Marie-Helene Marion</name><affiliation><inist:fA14 i1="07"><s1>Department of Neurology, St George's Hospital</s1><s2>London</s2><s3>GBR</s3><sZ>10 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Lewthwaite, Alistair J" sort="Lewthwaite, Alistair J" uniqKey="Lewthwaite A" first="Alistair J." last="Lewthwaite">Alistair J. Lewthwaite</name><affiliation><inist:fA14 i1="05"><s1>School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham</s1><s2>Birmingham</s2><s3>GBR</s3><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="08"><s1>University Hospitals Birmingham NHS Trust</s1><s2>Birmingham</s2><s3>GBR</s3><sZ>11 aut.</sZ><sZ>14 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="09"><s1>Department of Molecular Neuroscience, Institute of Neurology, University College London</s1><s2>London</s2><s3>GBR</s3><sZ>11 aut.</sZ><sZ>13 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Nicholl, David J" sort="Nicholl, David J" uniqKey="Nicholl D" first="David J." last="Nicholl">David J. Nicholl</name><affiliation><inist:fA14 i1="05"><s1>School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham</s1><s2>Birmingham</s2><s3>GBR</s3><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="06"><s1>Sandwell and West Birmingham Hospitals NHS Trust</s1><s3>GBR</s3><sZ>9 aut.</sZ><sZ>12 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="10"><s1>City Hospital</s1><s2>Birmingham</s2><s3>GBR</s3><sZ>12 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Wood, Nicholas W" sort="Wood, Nicholas W" uniqKey="Wood N" first="Nicholas W." last="Wood">Nicholas W. Wood</name><affiliation><inist:fA14 i1="09"><s1>Department of Molecular Neuroscience, Institute of Neurology, University College London</s1><s2>London</s2><s3>GBR</s3><sZ>11 aut.</sZ><sZ>13 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Morrison, Karen E" sort="Morrison, Karen E" uniqKey="Morrison K" first="Karen E." last="Morrison">Karen E. Morrison</name><affiliation><inist:fA14 i1="05"><s1>School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham</s1><s2>Birmingham</s2><s3>GBR</s3><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="08"><s1>University Hospitals Birmingham NHS Trust</s1><s2>Birmingham</s2><s3>GBR</s3><sZ>11 aut.</sZ><sZ>14 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Williams Gray, Caroline H" sort="Williams Gray, Caroline H" uniqKey="Williams Gray C" first="Caroline H." last="Williams-Gray">Caroline H. Williams-Gray</name><affiliation><inist:fA14 i1="11"><s1>Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's, Hospital, Hills Road</s1><s2>Cambridge</s2><s3>GBR</s3><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Evans, Jonathan R" sort="Evans, Jonathan R" uniqKey="Evans J" first="Jonathan R." last="Evans">Jonathan R. Evans</name><affiliation><inist:fA14 i1="11"><s1>Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's, Hospital, Hills Road</s1><s2>Cambridge</s2><s3>GBR</s3><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Sawcer, Stephen J" sort="Sawcer, Stephen J" uniqKey="Sawcer S" first="Stephen J." last="Sawcer">Stephen J. Sawcer</name><affiliation><inist:fA14 i1="11"><s1>Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's, Hospital, Hills Road</s1><s2>Cambridge</s2><s3>GBR</s3><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Barker, Roger A" sort="Barker, Roger A" uniqKey="Barker R" first="Roger A." last="Barker">Roger A. Barker</name><affiliation><inist:fA14 i1="11"><s1>Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's, Hospital, Hills Road</s1><s2>Cambridge</s2><s3>GBR</s3><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Wickremaratchi, Mirdhu M" sort="Wickremaratchi, Mirdhu M" uniqKey="Wickremaratchi M" first="Mirdhu M." last="Wickremaratchi">Mirdhu M. Wickremaratchi</name><affiliation><inist:fA14 i1="12"><s1>Department of Neurology, Worthing Hospital</s1><s2>Worthing</s2><s3>GBR</s3><sZ>19 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Ben Shlomo, Yoav" sort="Ben Shlomo, Yoav" uniqKey="Ben Shlomo Y" first="Yoav" last="Ben-Shlomo">Yoav Ben-Shlomo</name><affiliation><inist:fA14 i1="13"><s1>School of Social and Community Medicine, Bristol University</s1><s2>Bristol</s2><s3>GBR</s3><sZ>20 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Williams, Nigel M" sort="Williams, Nigel M" uniqKey="Williams N" first="Nigel M." last="Williams">Nigel M. Williams</name><affiliation><inist:fA14 i1="01"><s1>MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Neurology, School of Medicine, Cardiff University</s1><s2>Cardiff</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>21 aut.</sZ><sZ>22 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Morris, Huw R" sort="Morris, Huw R" uniqKey="Morris H" first="Huw R." last="Morris">Huw R. Morris</name><affiliation><inist:fA14 i1="01"><s1>MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Neurology, School of Medicine, Cardiff University</s1><s2>Cardiff</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>21 aut.</sZ><sZ>22 aut.</sZ></inist:fA14></affiliation></author></analytic><series><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Nervous system diseases</term><term>Parkin</term><term>Parkinson disease</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Maladie de Parkinson</term><term>Pathologie du système nerveux</term><term>Parkine</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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), PINK <sub>1</sub>, 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.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0885-3185</s0></fA01><fA03 i2="1"><s0>Mov. disord.</s0></fA03><fA05><s2>27</s2></fA05><fA06><s2>12</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Systematic Review and UK-Based Study of PARK2 (parkin), PINK1, PARK7 (DJ-1) and LRRK2 in Early-Onset Parkinson's Disease</s1></fA08><fA11 i1="01" i2="1"><s1>KILARSKI (Laura L.)</s1></fA11><fA11 i1="02" i2="1"><s1>PEARSON (Justin P.)</s1></fA11><fA11 i1="03" i2="1"><s1>NEWSWAY (Victoria)</s1></fA11><fA11 i1="04" i2="1"><s1>MAJOUNIE (Elisa)</s1></fA11><fA11 i1="05" i2="1"><s1>KNIPE (M. Duleeka W.)</s1></fA11><fA11 i1="06" i2="1"><s1>MISBAHUDDIN (Anjum)</s1></fA11><fA11 i1="07" i2="1"><s1>CHINNERY (Patrick F.)</s1></fA11><fA11 i1="08" i2="1"><s1>BURN (David J.)</s1></fA11><fA11 i1="09" i2="1"><s1>CLARKE (Carl E.)</s1></fA11><fA11 i1="10" i2="1"><s1>MARION (Marie-Helene)</s1></fA11><fA11 i1="11" i2="1"><s1>LEWTHWAITE (Alistair J.)</s1></fA11><fA11 i1="12" i2="1"><s1>NICHOLL (David J.)</s1></fA11><fA11 i1="13" i2="1"><s1>WOOD (Nicholas W.)</s1></fA11><fA11 i1="14" i2="1"><s1>MORRISON (Karen E.)</s1></fA11><fA11 i1="15" i2="1"><s1>WILLIAMS-GRAY (Caroline H.)</s1></fA11><fA11 i1="16" i2="1"><s1>EVANS (Jonathan R.)</s1></fA11><fA11 i1="17" i2="1"><s1>SAWCER (Stephen J.)</s1></fA11><fA11 i1="18" i2="1"><s1>BARKER (Roger A.)</s1></fA11><fA11 i1="19" i2="1"><s1>WICKREMARATCHI (Mirdhu M.)</s1></fA11><fA11 i1="20" i2="1"><s1>BEN-SHLOMO (Yoav)</s1></fA11><fA11 i1="21" i2="1"><s1>WILLIAMS (Nigel M.)</s1></fA11><fA11 i1="22" i2="1"><s1>MORRIS (Huw R.)</s1></fA11><fA14 i1="01"><s1>MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Neurology, School of Medicine, Cardiff University</s1><s2>Cardiff</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>21 aut.</sZ><sZ>22 aut.</sZ></fA14><fA14 i1="02"><s1>Department of Neurology, School of Medicine, Cardiff University</s1><s2>Cardiff</s2><s3>GBR</s3><sZ>5 aut.</sZ></fA14><fA14 i1="03"><s1>Department of Neurology, Barking, Havering & Redbridge University Hospitals NHS Trust</s1><s3>GBR</s3><sZ>6 aut.</sZ></fA14><fA14 i1="04"><s1>Institute of Genetic Medicine, Newcastle University, Central Parkway</s1><s2>Newcastle upon Tyne</s2><s3>GBR</s3><sZ>7 aut.</sZ><sZ>8 aut.</sZ></fA14><fA14 i1="05"><s1>School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham</s1><s2>Birmingham</s2><s3>GBR</s3><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ></fA14><fA14 i1="06"><s1>Sandwell and West Birmingham Hospitals NHS Trust</s1><s3>GBR</s3><sZ>9 aut.</sZ><sZ>12 aut.</sZ></fA14><fA14 i1="07"><s1>Department of Neurology, St George's Hospital</s1><s2>London</s2><s3>GBR</s3><sZ>10 aut.</sZ></fA14><fA14 i1="08"><s1>University Hospitals Birmingham NHS Trust</s1><s2>Birmingham</s2><s3>GBR</s3><sZ>11 aut.</sZ><sZ>14 aut.</sZ></fA14><fA14 i1="09"><s1>Department of Molecular Neuroscience, Institute of Neurology, University College London</s1><s2>London</s2><s3>GBR</s3><sZ>11 aut.</sZ><sZ>13 aut.</sZ></fA14><fA14 i1="10"><s1>City Hospital</s1><s2>Birmingham</s2><s3>GBR</s3><sZ>12 aut.</sZ></fA14><fA14 i1="11"><s1>Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's, Hospital, Hills Road</s1><s2>Cambridge</s2><s3>GBR</s3><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ></fA14><fA14 i1="12"><s1>Department of Neurology, Worthing Hospital</s1><s2>Worthing</s2><s3>GBR</s3><sZ>19 aut.</sZ></fA14><fA14 i1="13"><s1>School of Social and Community Medicine, Bristol University</s1><s2>Bristol</s2><s3>GBR</s3><sZ>20 aut.</sZ></fA14><fA20><s1>1522-1529</s1></fA20><fA21><s1>2012</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>20953</s2><s5>354000502081650100</s5></fA43><fA44><s0>0000</s0><s1>© 2012 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>39 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>12-0423953</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Movement disorders</s0></fA64><fA66 i1="01"><s0>USA</s0></fA66><fC01 i1="01" l="ENG"><s0>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), PINK <sub>1</sub>, 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.</s0></fC01><fC02 i1="01" i2="X"><s0>002B17</s0></fC02><fC02 i1="02" i2="X"><s0>002B17G</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Maladie de Parkinson</s0><s2>NM</s2><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Parkinson disease</s0><s2>NM</s2><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Parkinson enfermedad</s0><s2>NM</s2><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Pathologie du système nerveux</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Nervous system diseases</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Sistema nervioso patología</s0><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Parkine</s0><s5>09</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Parkin</s0><s5>09</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Parkin</s0><s5>09</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Pathologie de l'encéphale</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Cerebral disorder</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Encéfalo patología</s0><s5>37</s5></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Syndrome extrapyramidal</s0><s5>38</s5></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Extrapyramidal syndrome</s0><s5>38</s5></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Extrapiramidal síndrome</s0><s5>38</s5></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Maladie dégénérative</s0><s5>39</s5></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Degenerative disease</s0><s5>39</s5></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Enfermedad degenerativa</s0><s5>39</s5></fC07><fC07 i1="04" i2="X" l="FRE"><s0>Pathologie du système nerveux central</s0><s5>40</s5></fC07><fC07 i1="04" i2="X" l="ENG"><s0>Central nervous system disease</s0><s5>40</s5></fC07><fC07 i1="04" i2="X" l="SPA"><s0>Sistema nervosio central patología</s0><s5>40</s5></fC07><fN21><s1>331</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard><server><NO>PASCAL 12-0423953 INIST</NO><ET>Systematic Review and UK-Based Study of PARK2 (parkin), PINK1, PARK7 (DJ-1) and LRRK2 in Early-Onset Parkinson's Disease</ET><AU>KILARSKI (Laura L.); PEARSON (Justin P.); NEWSWAY (Victoria); MAJOUNIE (Elisa); KNIPE (M. Duleeka W.); MISBAHUDDIN (Anjum); CHINNERY (Patrick F.); BURN (David J.); CLARKE (Carl E.); MARION (Marie-Helene); LEWTHWAITE (Alistair J.); NICHOLL (David J.); WOOD (Nicholas W.); MORRISON (Karen E.); WILLIAMS-GRAY (Caroline H.); EVANS (Jonathan R.); SAWCER (Stephen J.); BARKER (Roger A.); WICKREMARATCHI (Mirdhu M.); BEN-SHLOMO (Yoav); WILLIAMS (Nigel M.); MORRIS (Huw R.)</AU><AF>MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Neurology, School of Medicine, Cardiff University/Cardiff/Royaume-Uni (1 aut., 2 aut., 3 aut., 4 aut., 21 aut., 22 aut.); Department of Neurology, School of Medicine, Cardiff University/Cardiff/Royaume-Uni (5 aut.); Department of Neurology, Barking, Havering & Redbridge University Hospitals NHS Trust/Royaume-Uni (6 aut.); Institute of Genetic Medicine, Newcastle University, Central Parkway/Newcastle upon Tyne/Royaume-Uni (7 aut., 8 aut.); School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham/Birmingham/Royaume-Uni (9 aut., 11 aut., 12 aut., 14 aut.); Sandwell and West Birmingham Hospitals NHS Trust/Royaume-Uni (9 aut., 12 aut.); Department of Neurology, St George's Hospital/London/Royaume-Uni (10 aut.); University Hospitals Birmingham NHS Trust/Birmingham/Royaume-Uni (11 aut., 14 aut.); Department of Molecular Neuroscience, Institute of Neurology, University College London/London/Royaume-Uni (11 aut., 13 aut.); City Hospital/Birmingham/Royaume-Uni (12 aut.); Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's, Hospital, Hills Road/Cambridge/Royaume-Uni (15 aut., 16 aut., 17 aut., 18 aut.); Department of Neurology, Worthing Hospital/Worthing/Royaume-Uni (19 aut.); School of Social and Community Medicine, Bristol University/Bristol/Royaume-Uni (20 aut.)</AF><DT>Publication en série; Niveau analytique</DT><SO>Movement disorders; ISSN 0885-3185; Etats-Unis; Da. 2012; Vol. 27; No. 12; Pp. 1522-1529; Bibl. 39 ref.</SO><LA>Anglais</LA><EA>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), PINK <sub>1</sub>, 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.</EA><CC>002B17; 002B17G</CC><FD>Maladie de Parkinson; Pathologie du système nerveux; Parkine</FD><FG>Pathologie de l'encéphale; Syndrome extrapyramidal; Maladie dégénérative; Pathologie du système nerveux central</FG><ED>Parkinson disease; Nervous system diseases; Parkin</ED><EG>Cerebral disorder; Extrapyramidal syndrome; Degenerative disease; Central nervous system disease</EG><SD>Parkinson enfermedad; Sistema nervioso patología; Parkin</SD><LO>INIST-20953.354000502081650100</LO><ID>12-0423953</ID></server></inist></record>Pour manipuler ce document sous Unix (Dilib)
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