Department of Pathology, Hospital Universitari and Health Sciences Research Institute Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain.
Department of Neurology and Multidisciplinary Sleep Unit, Hospital Clínic de Barcelona, IDIBAPS, CIBERNED, Barcelona, Spain.
Parkinsonism Relat Disord. 2018 May;50:94-98. doi: 10.1016/j.parkreldis.2018.02.034. Epub 2018 Feb 21.
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.
葡萄糖脑苷脂酶（GBA）基因变异与路易体障碍（LBD）帕金森病（PD）和路易体痴呆（DLB）的发展有关。特发性 REM 睡眠行为障碍（IRBD）在大多数情况下代表前驱 LBD。我们研究了 GBA 变异是否在 IRBD 中过度表达，以及它们的存在是否缩短了向临床定义的 LBD 转化的时间。
通过 Sanger 法对 69 例经多导睡眠图（PSG）证实的 IRBD 患者和 84 例匹配对照的 GBA 编码外显子进行测序。
在 8 例（11.6%）IRBD 患者和 1 例（1.2%）对照中发现了 7 种错义变异（E326K、L444P、A446T、A318G、R329C、T369M、N370S）（P=0.026）。从 IRBD 诊断开始平均随访 8.9±3.8 年后，5 例携带 GBA 变异的患者发展为 LBD（3 例 DLB 和 2 例 PD），3 例仍无疾病。携带 GBA 变异的 IRBD 患者发生 LBD 的风险与无变异患者相似（对数秩检验，p=0.935）。
在 IRBD 中，1）与对照组相比，GBA 变异更为常见，2）与即将发生的 PD 和 DLB 相关，但 3）在 IRBD 诊断后，不能提示 LBD 的短期风险。携带 GBA 变异的 IRBD 患者可以通过疾病修饰干预进行研究，旨在恢复 GBA 代谢途径。
