Glucocerebrosidase gene variants are accumulated in idiopathic REM sleep behavior disorder

Glucocerebrosidase (GBA) gene variants are associated with the development of the Lewy body disorders (LBD) Parkinson disease (PD) and dementia with Lewy bodies (DLB). Idiopathic REM sleep behavior disorder (IRBD) represents prodromal LBD in most instances. We investigated whether GBA variants are o...

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Bibliographic Details
Published in:Parkinsonism & related disorders 2018-05, Vol.50, p.94-98
Main Authors: Gámez-Valero, Ana, Iranzo, Alex, Serradell, Monica, Vilas, Dolores, Santamaria, Joan, Gaig, Carles, Álvarez, Ramiro, Ariza, Aurelio, Tolosa, Eduardo, Beyer, Katrin
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Dementia with Lewy bodies
Disease Progression
Female
Follow-Up Studies
Glucocerebrosidase variants
Glucosylceramidase - genetics
Humans
Idiopathic rapid eye movement sleep disorder
Lewy Body Disease - genetics
Male
Middle Aged
Parkinson Disease - genetics
Parkinson's disease
Prodromal Symptoms
REM Sleep Behavior Disorder - genetics
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Summary:Glucocerebrosidase (GBA) gene variants are associated with the development of the Lewy body disorders (LBD) Parkinson disease (PD) and dementia with Lewy bodies (DLB). Idiopathic REM sleep behavior disorder (IRBD) represents prodromal LBD in most instances. We investigated whether GBA variants are overrepresented in IRBD and if their presence shortens the time to conversion to clinically-defined LBD. All GBA coding exons from 69 polysomnography-confirmed IRBD patients and 84 matched controls were sequenced by the Sanger method. Seven missense variants (E326K, L444P, A446T, A318G, R329C, T369M, N370S) were identified in eight (11.6%) IRBD patients and in one (1.2%) control (P = 0.026). After a mean follow-up of 8.9 ± 3.8 years from IRBD diagnosis, five subjects with GBA variants developed LBD (3 DLB and 2 PD) and three remained disease-free. The risk of developing a LBD was similar in IRBD subjects with GBA variants than in those without variants (log rank test, p = 0.935). In IRBD, GBA variants are 1) more frequent when compared to controls, 2) associated with impending PD and DLB but 3) not indicative of a short-term risk for LBD after IRBD diagnosis. IRBD patients carrying GBA variants could be studied with disease-modifying interventions aiming to restore the GBA metabolic pathway. •Glucocerebrosidase gene variants were identified in 12% of patients with idiopathic REM sleep behavior disorder.•Patients with idiopathic REM sleep behavior disorder carrying glucocerebrosidase gene variants can develop both Parkinson disease and dementia with Lewy bodies.•The risk for developing a clinically-defined Lewy body condition was similar in patients with idiopathic REM sleep behavior disorder with and without glucocerebrosidase gene variants.
ISSN:1353-8020
1873-5126
DOI:10.1016/j.parkreldis.2018.02.034