Clinical expression of LRRK2 G2019S mutations in the elderly
Identifieur interne : 000779 ( Main/Exploration ); précédent : 000778; suivant : 000780Clinical expression of LRRK2 G2019S mutations in the elderly
Auteurs : Marta San Luciano [États-Unis] ; Richard B. Lipton [États-Unis] ; Cuiling Wang [États-Unis] ; Mindy Katz [États-Unis] ; Molly E. Zimmerman [États-Unis] ; Amy E. Sanders [États-Unis] ; Laurie J. Ozelius [États-Unis] ; Susan B. Bressman [États-Unis] ; Rachel Saunders-Pullman [États-Unis]Source :
- Movement Disorders [ 0885-3185 ] ; 2010-11-15.
English descriptors
- KwdEn :
Abstract
Mutations in the leucine‐rich repeat kinase 2 gene (LRRK2, PARK8) are the most commonly identified monogenic etiology of Parkinson disease (PD). Over‐represented in the Ashkenazi Jewish population, these mutations are transmitted in an autosomal dominant manner with age‐dependent reduced penetrance. The natural history and penetrance of these mutations in the elderly is controversial and inadequately studied. We conducted a nested cohort study in a community‐based aging study (the Einstein Aging Study). Six elderly, initially nonmanifesting carriers (NMC) of the LRKK2 G2019S mutation were identified (average age 82.1 ± 7.0, range 72.7–90.8), and five had available longitudinal data. We matched five noncarrier controls to each NMC and followed them for an average of 4.7 years with annual cognitive and motor examinations. PD was identified in one NMC at age 95 and in no control subjects. The remaining carriers did not differ from controls on motor scores at baseline or follow‐up. The baseline Unified Parkinson's Disease Rating Scale motor subscore (UPDRS‐III) in cases was 6.2 ± 6.9 (range 1–19) and in controls was 4.5 ± 6.6 (1–30), P = 0.6; the mean difference in UPDRS‐III slopes over time between cases and controls was 0.1 ± 1.3 and was not statistically significant. Our data, while limited by a small sample size, show that in LRKK2 G2019S mutation carriers, phenoconversion to PD can occur late in life. However, most NMC have motor decline which is indistinguishable from their age mates, suggesting that the larger subset of elderly NMC is not on the motor trajectory to disease. © 2010 Movement Disorder Society.
Url:
DOI: 10.1002/mds.23330
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Clinical expression of LRRK2 G2019S mutations in the elderly</title><author><name sortKey="Luciano, Marta San" sort="Luciano, Marta San" uniqKey="Luciano M" first="Marta San" last="Luciano">Marta San Luciano</name></author><author><name sortKey="Lipton, Richard B" sort="Lipton, Richard B" uniqKey="Lipton R" first="Richard B." last="Lipton">Richard B. Lipton</name></author><author><name sortKey="Wang, Cuiling" sort="Wang, Cuiling" uniqKey="Wang C" first="Cuiling" last="Wang">Cuiling Wang</name></author><author><name sortKey="Katz, Mindy" sort="Katz, Mindy" uniqKey="Katz M" first="Mindy" last="Katz">Mindy Katz</name></author><author><name sortKey="Zimmerman, Molly E" sort="Zimmerman, Molly E" uniqKey="Zimmerman M" first="Molly E." last="Zimmerman">Molly E. Zimmerman</name></author><author><name sortKey="Sanders, Amy E" sort="Sanders, Amy E" uniqKey="Sanders A" first="Amy E." last="Sanders">Amy E. Sanders</name></author><author><name sortKey="Ozelius, Laurie J" sort="Ozelius, Laurie J" uniqKey="Ozelius L" first="Laurie J." last="Ozelius">Laurie J. Ozelius</name></author><author><name sortKey="Bressman, Susan B" sort="Bressman, Susan B" uniqKey="Bressman S" first="Susan B." last="Bressman">Susan B. Bressman</name></author><author><name sortKey="Saunders Ullman, Rachel" sort="Saunders Ullman, Rachel" uniqKey="Saunders Ullman R" first="Rachel" last="Saunders-Pullman">Rachel Saunders-Pullman</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:0DC594855AEFC95767504F8F2E45C23B600BF032</idno><date when="2010" year="2010">2010</date><idno type="doi">10.1002/mds.23330</idno><idno type="url">https://api.istex.fr/document/0DC594855AEFC95767504F8F2E45C23B600BF032/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">000945</idno><idno type="wicri:Area/Main/Curation">000821</idno><idno type="wicri:Area/Main/Exploration">000779</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Clinical expression of LRRK2 G2019S mutations in the elderly</title><author><name sortKey="Luciano, Marta San" sort="Luciano, Marta San" uniqKey="Luciano M" first="Marta San" last="Luciano">Marta San Luciano</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Beth Israel Medical Center, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Lipton, Richard B" sort="Lipton, Richard B" uniqKey="Lipton R" first="Richard B." last="Lipton">Richard B. Lipton</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Albert Einstein College of Medicine, Bronx, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Wang, Cuiling" sort="Wang, Cuiling" uniqKey="Wang C" first="Cuiling" last="Wang">Cuiling Wang</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Katz, Mindy" sort="Katz, Mindy" uniqKey="Katz M" first="Mindy" last="Katz">Mindy Katz</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Albert Einstein College of Medicine, Bronx, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Zimmerman, Molly E" sort="Zimmerman, Molly E" uniqKey="Zimmerman M" first="Molly E." last="Zimmerman">Molly E. Zimmerman</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Albert Einstein College of Medicine, Bronx, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Sanders, Amy E" sort="Sanders, Amy E" uniqKey="Sanders A" first="Amy E." last="Sanders">Amy E. Sanders</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Albert Einstein College of Medicine, Bronx, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Ozelius, Laurie J" sort="Ozelius, Laurie J" uniqKey="Ozelius L" first="Laurie J." last="Ozelius">Laurie J. Ozelius</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Mount Sinai School of Medicine, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Bressman, Susan B" sort="Bressman, Susan B" uniqKey="Bressman S" first="Susan B." last="Bressman">Susan B. Bressman</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Beth Israel Medical Center, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Albert Einstein College of Medicine, Bronx, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Saunders Ullman, Rachel" sort="Saunders Ullman, Rachel" uniqKey="Saunders Ullman R" first="Rachel" last="Saunders-Pullman">Rachel Saunders-Pullman</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Beth Israel Medical Center, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Albert Einstein College of Medicine, Bronx, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Movement Disorders</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2010-11-15">2010-11-15</date><biblScope unit="volume">25</biblScope><biblScope unit="issue">15</biblScope><biblScope unit="page" from="2571">2571</biblScope><biblScope unit="page" to="2576">2576</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">0DC594855AEFC95767504F8F2E45C23B600BF032</idno><idno type="DOI">10.1002/mds.23330</idno><idno type="ArticleID">MDS23330</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>LRRK2</term><term>Parkinson's disease</term><term>clinical</term><term>cognition</term><term>nonmanifesting carriers</term><term>parkinsonism</term><term>penetrance</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Mutations in the leucine‐rich repeat kinase 2 gene (LRRK2, PARK8) are the most commonly identified monogenic etiology of Parkinson disease (PD). Over‐represented in the Ashkenazi Jewish population, these mutations are transmitted in an autosomal dominant manner with age‐dependent reduced penetrance. The natural history and penetrance of these mutations in the elderly is controversial and inadequately studied. We conducted a nested cohort study in a community‐based aging study (the Einstein Aging Study). Six elderly, initially nonmanifesting carriers (NMC) of the LRKK2 G2019S mutation were identified (average age 82.1 ± 7.0, range 72.7–90.8), and five had available longitudinal data. We matched five noncarrier controls to each NMC and followed them for an average of 4.7 years with annual cognitive and motor examinations. PD was identified in one NMC at age 95 and in no control subjects. The remaining carriers did not differ from controls on motor scores at baseline or follow‐up. The baseline Unified Parkinson's Disease Rating Scale motor subscore (UPDRS‐III) in cases was 6.2 ± 6.9 (range 1–19) and in controls was 4.5 ± 6.6 (1–30), P = 0.6; the mean difference in UPDRS‐III slopes over time between cases and controls was 0.1 ± 1.3 and was not statistically significant. Our data, while limited by a small sample size, show that in LRKK2 G2019S mutation carriers, phenoconversion to PD can occur late in life. However, most NMC have motor decline which is indistinguishable from their age mates, suggesting that the larger subset of elderly NMC is not on the motor trajectory to disease. © 2010 Movement Disorder Society.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>État de New York</li></region></list><tree><country name="États-Unis"><region name="État de New York"><name sortKey="Luciano, Marta San" sort="Luciano, Marta San" uniqKey="Luciano M" first="Marta San" last="Luciano">Marta San Luciano</name></region><name sortKey="Bressman, Susan B" sort="Bressman, Susan B" uniqKey="Bressman S" first="Susan B." last="Bressman">Susan B. Bressman</name><name sortKey="Bressman, Susan B" sort="Bressman, Susan B" uniqKey="Bressman S" first="Susan B." last="Bressman">Susan B. Bressman</name><name sortKey="Katz, Mindy" sort="Katz, Mindy" uniqKey="Katz M" first="Mindy" last="Katz">Mindy Katz</name><name sortKey="Lipton, Richard B" sort="Lipton, Richard B" uniqKey="Lipton R" first="Richard B." last="Lipton">Richard B. Lipton</name><name sortKey="Ozelius, Laurie J" sort="Ozelius, Laurie J" uniqKey="Ozelius L" first="Laurie J." last="Ozelius">Laurie J. Ozelius</name><name sortKey="Ozelius, Laurie J" sort="Ozelius, Laurie J" uniqKey="Ozelius L" first="Laurie J." last="Ozelius">Laurie J. Ozelius</name><name sortKey="Sanders, Amy E" sort="Sanders, Amy E" uniqKey="Sanders A" first="Amy E." last="Sanders">Amy E. Sanders</name><name sortKey="Saunders Ullman, Rachel" sort="Saunders Ullman, Rachel" uniqKey="Saunders Ullman R" first="Rachel" last="Saunders-Pullman">Rachel Saunders-Pullman</name><name sortKey="Saunders Ullman, Rachel" sort="Saunders Ullman, Rachel" uniqKey="Saunders Ullman R" first="Rachel" last="Saunders-Pullman">Rachel Saunders-Pullman</name><name sortKey="Wang, Cuiling" sort="Wang, Cuiling" uniqKey="Wang C" first="Cuiling" last="Wang">Cuiling Wang</name><name sortKey="Zimmerman, Molly E" sort="Zimmerman, Molly E" uniqKey="Zimmerman M" first="Molly E." last="Zimmerman">Molly E. Zimmerman</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000779 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000779 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= ParkinsonV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= ISTEX:0DC594855AEFC95767504F8F2E45C23B600BF032
|texte= Clinical expression of LRRK2 G2019S mutations in the elderly
}}
| This area was generated with Dilib version V0.6.23. |  |