Clinical expression of LRRK2 G2019S mutations in the elderly

Marta San Luciano, Richard B. Lipton, Cuiling Wang, Mindy Joy Katz, Molly E. Zimmerman, Amy E. Sanders, Laurie J. Ozelius, Susan B. Bressman, Rachel Saunders-Pullman

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)2571-2576
Number of pages6
JournalMovement Disorders
Volume25
Issue number15
DOIs
StatePublished - Nov 2010

Fingerprint

Parkinson Disease
Mutation
Penetrance
Natural History
Leucine
Sample Size
Cohort Studies
Phosphotransferases
Population
Genes

Keywords

  • Clinical
  • Cognition
  • LRRK2
  • Nonmanifesting carriers
  • Parkinson's disease
  • Parkinsonism
  • Penetrance

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Luciano, M. S., Lipton, R. B., Wang, C., Katz, M. J., Zimmerman, M. E., Sanders, A. E., ... Saunders-Pullman, R. (2010). Clinical expression of LRRK2 G2019S mutations in the elderly. Movement Disorders, 25(15), 2571-2576. https://doi.org/10.1002/mds.23330

Clinical expression of LRRK2 G2019S mutations in the elderly. / Luciano, Marta San; Lipton, Richard B.; Wang, Cuiling; Katz, Mindy Joy; Zimmerman, Molly E.; Sanders, Amy E.; Ozelius, Laurie J.; Bressman, Susan B.; Saunders-Pullman, Rachel.

In: Movement Disorders, Vol. 25, No. 15, 11.2010, p. 2571-2576.

Research output: Contribution to journalArticle

Luciano, MS, Lipton, RB, Wang, C, Katz, MJ, Zimmerman, ME, Sanders, AE, Ozelius, LJ, Bressman, SB & Saunders-Pullman, R 2010, 'Clinical expression of LRRK2 G2019S mutations in the elderly', Movement Disorders, vol. 25, no. 15, pp. 2571-2576. https://doi.org/10.1002/mds.23330
Luciano, Marta San ; Lipton, Richard B. ; Wang, Cuiling ; Katz, Mindy Joy ; Zimmerman, Molly E. ; Sanders, Amy E. ; Ozelius, Laurie J. ; Bressman, Susan B. ; Saunders-Pullman, Rachel. / Clinical expression of LRRK2 G2019S mutations in the elderly. In: Movement Disorders. 2010 ; Vol. 25, No. 15. pp. 2571-2576.
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