Glucocerebrosidase gene variants are accumulated in idiopathic REM sleep behavior disorder

被引：22

作者：

Gamez-Valero, Ana ^{[1
]}

Iranzo, Alex ^{[2
,3
]}

Serradell, Monica ^{[2
,3
]}

Vilas, Dolores ^{[4
]}

Santamaria, Joan ^{[2
,3
]}

Gaig, Caries ^{[2
,3
]}

Alvarez, Ramiro ^{[4
]}

Ariza, Aurelio ^{[1
]}

Tolosa, Eduardo ^{[5
]}

Beyer, Katrin ^{[1
]}

机构：

[1] Univ Autonoma Barcelona, Hosp Univ & Hlth Sci, Res Inst Germans Trias & Pujol, Dept Pathol, Barcelona, Spain

[2] Hosp Clin Barcelona, IDIBAPS, CIBERNED, Dept Neurol, Barcelona, Spain

[3] Hosp Clin Barcelona, IDIBAPS, CIBERNED, Multidisciplinary Sleep Unit, Barcelona, Spain

[4] Hosp Badalona Germans Trias & Pujol, Dept Neurol, Barcelona, Spain

[5] Univ Barcelona, Hosp Clin Barcelona, CIBERNED, Movement Disorders Unit,Neurol Serv,IDIBAPS, Barcelona, Spain

来源：

PARKINSONISM & RELATED DISORDERS | 2018年 / 50卷

关键词：

Glucocerebrosidase variants; Idiopathic rapid eye movement sleep disorder; Parkinson's disease; Dementia with Lewy bodies; NEURODEGENERATIVE DISEASE; PARKINSONS-DISEASE; GAUCHER-DISEASE; MUTATIONS; DIAGNOSIS; DEMENTIA; GBA; POLYMORPHISM; ASSOCIATION; MULTICENTER;

D O I：

10.1016/j.parkreldis.2018.02.034

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Introduction: 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. Methods: All GBA coding exons from 69 polysomnography-confirmed IRBD patients and 84 matched controls were sequenced by the Sanger method. Results: Seven missense variants (E326K, L444P, A446T, A318G, R329C, T369M, N3705) 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). Conclusions: 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. (C) 2018 Elsevier Ltd. All rights reserved.

引用

页码：94 / 98

页数：5

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