GBA variants in REM sleep behavior disorder: A multicenter study

. 2020 Aug 25 ; 95 (8) : e1008-e1016. [epub] 20200626

Jazyk angličtina Země Spojené státy americké Médium print-electronic

Typ dokumentu časopisecké články, multicentrická studie, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/pmid32591474

Grantová podpora
Department of Health - United Kingdom
CIHR - Canada
MR/L023784/1 Medical Research Council - United Kingdom
J-0901 Parkinson's UK - United Kingdom
MC_EX_MR/N50192X/1 Medical Research Council - United Kingdom
MR/M024962/1 Medical Research Council - United Kingdom
U01 NS100620 NINDS NIH HHS - United States

Odkazy

PubMed 32591474
PubMed Central PMC7668554
DOI 10.1212/wnl.0000000000010042
PII: WNL.0000000000010042
Knihovny.cz E-zdroje

OBJECTIVE: To study the role of GBA variants in the risk for isolated REM sleep behavior disorder (iRBD) and conversion to overt neurodegeneration. METHODS: A total of 4,147 individuals were included: 1,061 patients with iRBD and 3,086 controls. GBA was fully sequenced using molecular inversion probes and Sanger sequencing. We analyzed the effects of GBA variants on the risk of iRBD, age at onset (AAO), and conversion rates. RESULTS: GBA variants were found in 9.5% of patients with iRBD compared to 4.1% of controls (odds ratio, 2.45; 95% confidence interval [CI], 1.87-3.22; p = 1 × 10-10). The estimated OR for mild p.N370S variant carriers was 3.69 (95% CI, 1.90-7.14; p = 3.5 × 10-5), while for severe variant carriers it was 17.55 (95% CI, 2.11-145.9; p = 0.0015). Carriers of severe GBA variants had an average AAO of 52.8 years, 7-8 years earlier than those with mild variants or noncarriers (p = 0.029). Of the GBA variant carriers with available data, 52.5% had converted, compared to 35.6% of noncarriers (p = 0.011), with a trend for faster conversion among severe GBA variant carriers. However, the results on AAO and conversion were based on small numbers and should be interpreted with caution. CONCLUSIONS: GBA variants robustly and differentially increase the risk of iRBD. The rate of conversion to neurodegeneration is also increased and may be faster among severe GBA variant carriers, although confirmation will be required in larger samples. Screening for RBD in healthy carriers of GBA variants should be studied as a potential way to identify GBA variant carriers who will develop a synucleinopathy in the future.

Zobrazit více v PubMed

Hogl B, Stefani A, Videnovic A. Idiopathic REM sleep behaviour disorder and neurodegeneration: an update. Nat Rev Neurol 2018;14:40–55. PubMed

Postuma RB, Iranzo A, Hu M, et al. . Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study. Brain 2019;142:744–759. PubMed PMC

Yao C, Fereshtehnejad SM, Dawson BK, et al. . Longstanding disease-free survival in idiopathic REM sleep behavior disorder: is neurodegeneration inevitable? Parkinsonism Relat Disord 2018;54:99–102. PubMed

Iranzo A, Stefani A, Serradell M, et al. . Characterization of patients with longstanding idiopathic REM sleep behavior disorder. Neurology 2017;89:242–248. PubMed

Gan-Or Z, Amshalom I, Kilarski LL, et al. . Differential effects of severe vs mild GBA mutations on Parkinson disease. Neurology 2015;84:880–887. PubMed PMC

Sidransky E, Nalls MA, Aasly JO, et al. . Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease. N Engl J Med 2009;361:1651–1661. PubMed PMC

Nalls MA, Duran R, Lopez G, et al. . A multicenter study of glucocerebrosidase mutations in dementia with Lewy bodies. JAMA Neurol 2013;70:727–735. PubMed PMC

Mitsui J, Matsukawa T, Sasaki H, et al. . Variants associated with Gaucher disease in multiple system atrophy. Ann Clin Transl Neurol 2015;2:417–426. PubMed PMC

Sailer A, Scholz SW, Nalls MA, et al. . A genome-wide association study in multiple system atrophy. Neurology 2016;87:1591–1598. PubMed PMC

Sklerov M, Kang UJ, Liong C, et al. . Frequency of GBA variants in autopsy-proven multiple system atrophy. Mov Disord Clin Pract 2017;4:574–581. PubMed PMC

Gan-Or Z, Liong C, Alcalay RN. GBA-associated Parkinson's disease and other synucleinopathies. Curr Neurol Neurosci Rep 2018;18:44. PubMed

Beutler E, Gelbart T, Scott CR. Hematologically important mutations: Gaucher disease. Blood Cell Mol Dis 2005;35:355–364. PubMed

Cilia R, Tunesi S, Marotta G, et al. . Survival and dementia in GBA-associated Parkinson's disease: the mutation matters. Ann Neurol 2016;80:662–673. PubMed

Liu G, Boot B, Locascio JJ, et al. . Specifically neuropathic Gaucher's mutations accelerate cognitive decline in Parkinson's. Ann Neurol 2016;80:674–685. PubMed PMC

Gan-Or Z, Mirelman A, Postuma RB, et al. . GBA mutations are associated with rapid eye movement sleep behavior disorder. Ann Clin Transl Neurol 2015;2:941–945. PubMed PMC

Gamez-Valero A, Iranzo A, Serradell M, et al. . Glucocerebrosidase gene variants are accumulated in idiopathic REM sleep behavior disorder. Parkinsonism Relat Disord 2018;50:94–98. PubMed

Honeycutt L, Montplaisir JY, Gagnon JF, et al. . Glucocerebrosidase mutations and phenoconversion of REM sleep behavior disorder to parkinsonism and dementia. Parkinsonism Relat Disord 2019;65:230–233. PubMed

Hogl B, Stefani A. REM sleep behavior disorder (RBD): update on diagnosis and treatment. Somnologie 2017;21:1–8. PubMed PMC

Ruskey JA, Zhou S, Santiago R, et al. . The GBA p.Trp378Gly mutation is a probable French-Canadian founder mutation causing Gaucher disease and synucleinopathies. Clin Genet 2018;94:339–345. PubMed

Blauwendraat C, Bras JM, Nalls MA, et al. . Coding variation in GBA explains the majority of the SYT11-GBA Parkinson's disease GWAS locus. Mov Disord 2018;33:1821–1823. PubMed PMC

Mallett V, Ross JP, Alcalay RN, et al. . GBA p.T369M substitution in Parkinson disease: polymorphism or association? A meta-analysis. Neurol Genet 2016;2:e104. PubMed PMC

Barber TR, Lawton M, Rolinski M, et al. . Prodromal parkinsonism and neurodegenerative risk stratification in REM sleep behavior disorder. Sleep 2017;40. PubMed PMC

Berge-Seidl V, Pihlstrom L, Maple-Grodem J, et al. . The GBA variant E326K is associated with Parkinson's disease and explains a genome-wide association signal. Neurosci Lett 2017;658:48–52. PubMed

Gan-Or Z, Alcalay RN, Makarious MB, et al. . Classification of GBA variants and their effects in synucleinopathies. Mov Disord 2019;34:1581–1582. PubMed

Mazzulli JR, Xu YH, Sun Y, et al. . Gaucher disease glucocerebrosidase and alpha-synuclein form a bidirectional pathogenic loop in synucleinopathies. Cell 2011;146:37–52. PubMed PMC

Gan-Or Z, Dion PA, Rouleau GA. Genetic perspective on the role of the autophagy-lysosome pathway in Parkinson disease. Autophagy 2015;11:1443–1457. PubMed PMC

Osellame LD, Duchen MR. Defective quality control mechanisms and accumulation of damaged mitochondria link Gaucher and Parkinson diseases. Autophagy 2013;9:1633–1635. PubMed

Ron I, Rapaport D, Horowitz M. Interaction between parkin and mutant glucocerebrosidase variants: a possible link between Parkinson disease and Gaucher disease. Hum Mol Genet 2010;19:3771–3781. PubMed

Najít záznam

Citační ukazatele

Nahrávání dat ...

Možnosti archivace

Nahrávání dat ...