MovDisordV3, Main, Exploration, bibRecord, 001F66

Clinical Expression of LRRK2 G2019S Mutations in the Elderly

Identifieur interne : 001F66 ( Main/Exploration ); précédent : 001F65; suivant : 001F67

Clinical 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.

RBID : Pascal:10-0512939

Descripteurs français

Pascal (Inist)
- Maladie de Parkinson, Parkinsonisme, Pathologie du système nerveux, Mutation, Personne âgée, Porteur, Pénétrance génique, Cognition.
Wicri :
- topic : Personne âgée.

English descriptors

KwdEn :
- Carrier, Cognition, Elderly, Gene penetrance, Mutation, Nervous system diseases, Parkinson disease, Parkinsonism.

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.

Affiliations:

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Le document en format XML

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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Carrier</term>
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<keywords scheme="Pascal" xml:lang="fr"><term>Maladie de Parkinson</term>
<term>Parkinsonisme</term>
<term>Pathologie du   système nerveux</term>
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<term>Personne âgée</term>
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<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.</div>
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<name sortKey="Bressman, Susan B" sort="Bressman, Susan B" uniqKey="Bressman S" first="Susan B." last="Bressman">Susan B. Bressman</name>
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<name sortKey="Cuiling Wang" sort="Cuiling Wang" uniqKey="Cuiling Wang" last="Cuiling Wang">CUILING WANG</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>
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<name sortKey="Zimmerman, Molly E" sort="Zimmerman, Molly E" uniqKey="Zimmerman M" first="Molly E." last="Zimmerman">Molly E. Zimmerman</name>
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</tree>
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</record>

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   |texte=   Clinical Expression of LRRK2 G2019S Mutations in the Elderly
}}

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	Movement Disorders (revue)
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Movement Disorders (revue)

Clinical Expression of LRRK2 G2019S Mutations in the Elderly

Clinical Expression of LRRK2 G2019S Mutations in the Elderly

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