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TitleDecreased Penetrance of Parkinson's Disease in Elderly Carriers of Glucocerebrosidase Gene L444P/R Mutations: A Community-Based 10-Year Longitudinal Study.
Publication TypeJournal Article
Year of Publication2020
AuthorsJi, Shaozhen, Chaodong Wang, Hongwen Qiao, Zhuqin Gu, Ziv Gan-Or, Edward A. Fon, and Piu Chan
JournalMov Disord
Date Published2020 04

BACKGROUND: Heterozygous mutations in the glucocerebrosidase gene (GBA) have been shown to be an important genetic risk factor for Parkinson's disease (PD) worldwide. However, the penetrance of GBA heterozygote for L444P, the common mutation for Asian population, is not known in older Chinese people.

OBJECTIVES: To assess the conversion rate to PD in identified carriers of GBA L444P/R mutations in Chinese community-dwelling older adults.

METHODS: The GBA gene was sequenced for mutations at position 444 in 8405 people older than 55 years who participated in the Beijing Longitudinal Study on Aging II cohort. Nine subjects were identified as heterozygous carriers of GBA L444P or L444R mutations at baseline and clinically followed up from 2009 to 2019 to investigate their PD conversion, motor and nonmotor symptoms, and change of vesicular monoamine transporter type 2 using tracer of [ F]9-fluoropropyl-(+)-dihydrotetrabenazine ( F-DTBZ, also known as F-AV-133).

RESULTS: Eight heterozygous GBA L444P and 1 L444R mutation carriers were identified without PD at baseline, and none of them developed clinical parkinsonism after a 10-year follow-up.

CONCLUSIONS: Although GBA mutations may lead to an earlier onset PD, the majority of GBA L444P heterozygotes in older adults may not convert to PD. Further studies are warranted to identify factors that modify the risk of conversion. © 2020 International Parkinson and Movement Disorder Society.

Alternate JournalMov Disord
PubMed ID31912918
Grant ListSML20150803 / / Beijing Municipal Administration of Hospitals' Mission Plan / International
Z161100000216140 / / Beijing Municipal Science & Technology Commission / International
Z171100000117013 / / Beijing Municipal Science & Technology Commission / International
FDN - 154301 / / CIHR Foundation / International
2017YFC0840105 / / National Key R&D Program of China / International
2018YFC1312001 / / National Key R&D Program of China / International