Add like
Add dislike
Add to saved papers

High Frequency of GBA Gene Mutations in Dementia With Lewy Bodies Among Ashkenazi Jews.

JAMA Neurology 2016 December 2
IMPORTANCE: Mutations in the glucocerebrosidase (GBA) gene are a risk factor for the development of dementia with Lewy bodies (DLB). These mutations are common among Ashkenazi Jews (AJ) and appear to have an effect on the natural history of the disease.

OBJECTIVES: To evaluate the clinical and genetic characteristics of an AJ cohort of patients diagnosed with DLB, assess the association of phenotype of DLB with GBA mutations, and explore the effects of these mutations on the clinical course of the disease.

DESIGN, SETTING, AND PARTICIPANTS: Thirty-five consecutively recruited AJ patients with newly diagnosed clinically probable or possible DLB underwent genotyping for the 7 known AJ GBA mutations and the LRRK2 G2019S mutation. Two patients with the LRRK2 G2019S mutation were excluded from the final analysis. Data were collected from July 1, 2013, to July 31, 2015.

MAIN OUTCOMES AND MEASURES: Assessment of clinical markers included the following standardized scales: Autonomic Scale for Outcomes in Parkinson's Disease (SCOPA-AUT), REM (Rapid Eye Movement) Sleep Behavior Disorder Single-Question Screen, Geriatric Depression Scale, and Montreal Cognitive Assessment. Motor symptoms were assessed with the Unified Parkinson's Disease Rating Scale motor part III. A subset of 15 patients also underwent assessment with the Color Trail Making Test, FAS verbal fluency, Digit Span, Hooper Visual Organization Test, and Stroop test.

RESULTS: Among the 35 patients with DLB (23 men [66%] and 12 women [34%]; mean [SD], 69.6 [8.2] years), 11 (31%) were carriers of mutations in the GBA gene. Among the 33 patients undergoing further analysis, the GBA mutation carriers were younger at symptom onset (mean [SD] age, 65.7 [11.7] vs 72.1 [5.1] years; P = .03), had more frequent visual hallucinations that did not achieve significance (9 of 11 [82%] compared with 12 of 22 [55%]; P = .052), and had higher scores on the RBD questionnaire (mean [SD], 7.8 [2.2] vs 5.1 [3.3]; P = .03). After adjusting for age and duration of symptoms, testing revealed that GBA mutation carriers had poorer cognition as assessed by the Montreal Cognitive Assessment Battery (mean [SD] score, 18.75 [5.99] vs 23.23 [3.16]; P = .03), lower scores on tests of verbal fluency (adjusted z scores, 0.50 vs -2.02; P = .02), worse scores on tests of visuospatial function (adjusted t scores, 68.55 vs 79.57; P = .046), and higher mean (SD) scores on the Unified Parkinson's Disease Rating Scale motor part III (36.72 [10.62] vs 25.72 [10.32]; P = .03).

CONCLUSIONS AND RELEVANCE: One in 3 AJ patients diagnosed with DLB were carriers of a GBA mutation, making it the most common genetic mutation identified in association with this disease and with any dementia disorder. Mutations in the GBA gene were associated with more severe motor and cognitive dysfunction, supporting a specific contribution of the GBA gene or lysosome function to this clinical syndrome.

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app