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. 2017 Oct;32(10):1432-1438.
doi: 10.1002/mds.27059. Epub 2017 Jun 22.

Penetrance estimate of LRRK2 p.G2019S mutation in individuals of non-Ashkenazi Jewish ancestry

Annie J Lee  1 , Yuanjia Wang  1 , Roy N Alcalay  2   3 , Helen Mejia-Santana  2 , Rachel Saunders-Pullman  4 , Susan Bressman  4 , Jean-Christophe Corvol  5   6   7   8   9   10 , Alexis Brice  5   6   7   8   9   10 , Suzanne Lesage  5   6   7   8   9   10 , Graziella Mangone  5   6   7   8   9   10 , Eduardo Tolosa  11   12   13 , Claustre Pont-Sunyer  11   12 , Dolores Vilas  11   12 , Birgitt Schüle  14 , Farah Kausar  14 , Tatiana Foroud  15 , Daniela Berg  16 , Kathrin Brockmann  17 , Stefano Goldwurm  18 , Chiara Siri  18 , Rosanna Asselta  19   20 , Javier Ruiz-Martinez  21   22 , Elisabet Mondragón  21   22 , Connie Marras  23 , Taneera Ghate  23 , Nir Giladi  24   25 , Anat Mirelman  24   25 , Karen Marder  2   3 ; Michael J. Fox LRRK2 Cohort Consortium
Affiliations

Penetrance estimate of LRRK2 p.G2019S mutation in individuals of non-Ashkenazi Jewish ancestry

Annie J Lee et al. Mov Disord. 2017 Oct.

Abstract

Background: Penetrance estimates of the leucine-rich repeat kinase 2 (LRRK2) p.G2019S mutation for PD vary widely (24%-100%). The p.G2019S penetrance in individuals of Ashkenazi Jewish ancestry has been estimated as 25%, adjusted for multiple covariates. It is unknown whether penetrance varies among different ethnic groups. The objective of this study was to estimate the penetrance of p.G2019S in individuals of non-Ashkenazi Jewish ancestry and compare penetrance between Ashkenazi Jews and non-Ashkenazi Jews to age 80.

Methods: The kin-cohort method was used to estimate penetrance in 474 first-degree relatives of 69 non-Ashkenazi Jewish LRRK2 p.G2019S carrier probands at 8 sites from the Michael J. Fox LRRK2 Cohort Consortium. An identical validated family history interview was administered to assess age at onset of PD, current age, or age at death for relatives in different ethnic groups at each site. Neurological examination and LRRK2 genotype of relatives were included when available.

Results: Risk of PD in non-Ashkenazi Jewish relatives who carry a LRRK2 p.G2019S mutation was 42.5% (95% confidence interval [CI]: 26.3%-65.8%) to age 80, which is not significantly higher than the previously estimated 25% (95% CI: 16.7%-34.2%) in Ashkenazi Jewish carrier relatives. The penetrance of PD to age 80 in LRRK2 p.G2019S mutation carrier relatives was significantly higher than the noncarrier relatives, as seen in Ashkenazi Jewish relatives.

Conclusions: The similar penetrance of LRRK2 p.G2019S estimated in Ashkenazi Jewish carriers and non-Ashkenazi Jewish carriers confirms that p.G2019S penetrance is 25% to 42.5% at age 80 in all populations analyzed. © 2017 International Parkinson and Movement Disorder Society.

Keywords: LRRK2; Parkinson's disease; penetrance.

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Conflict of interest statement

Conflict of Interest: No conflicts of interests to report with relevance to this publication.

Figures

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