Glucocerebrosidase gene mutations are associated with Parkinson's disease in Russia

Anton, Emil; Boukina, T.M.; Yakimovskii, A. F.; Usenko, T.; Drosdova, A.S.; Zakharchuk, A. G.; Andoskin, P.; Dubina, Michael; Schwarzman, A. L.; Pchelina, Sofya

doi:10.1002/mds.23950

Cited by 30 publications

(11 citation statements)

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“…Although parkinsonian symptoms in patients with Gaucher's disease were initially thought to be poorly responsive to levodopa treatment, 19 most subsequent studies have reported good or excellent responses, similar to those in patients with sporadic Parkinson’s disease. 17,30,34,39,41,62 …”

Section: Clinical Features Of Gba-associated Parkinsonismmentioning

confidence: 99%

The link between the GBA gene and parkinsonism

Sidransky

Lopez

2012

The Lancet Neurology

495

406

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Mutations in the glucocerebrosidase (GBA) gene, which encodes the lysosomal enzyme that is deficient in Gaucher's disease, are important and common risk factors for Parkinson’s disease and related disorders. This association was first recognised in the clinic, where parkinsonism was noted, albeit rarely, in patients with Gaucher's disease and more frequently in relatives who were obligate carriers. Subsequently, findings from large studies showed that patients with Parkinson’s disease and associated Lewy body disorders had an increased frequency of GBA mutations when compared with control individuals. Patients with GBA-associated parkinsonism exhibit varying parkinsonian phenotypes but tend to have an earlier age of onset and more associated cognitive changes than patients with parkinsonism without GBA mutations. Hypotheses proposed to explain this association include a gain-of-function due to mutations in glucocerebrosidase that promotes α-synuclein aggregation; substrate accumulation due to enzymatic loss-of-function, which affects α-synuclein processing and clearance; and a bidirectional feedback loop. Identification of the pathological mechanisms underlying GBA-associated parkinsonism will improve our understanding of the genetics, pathophysiology, and treatment for both rare and common neurological diseases.

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Section: Clinical Features Of Gba-associated Parkinsonismmentioning

confidence: 99%

The link between the GBA gene and parkinsonism

Sidransky

Lopez

2012

The Lancet Neurology

495

406

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“…Mutations in GBA (glucosidase, beta, acid), encoding the lysosomal enzyme glucocerebrosidase, are important risk factors for Parkinson disease (PD) worldwide. 1 Positive association between GBA mutations and PD was demonstrated in various populations, including Asians, [2][3][4][5][6] Europeans, [7][8][9][10][11][12] North Africans, 13 North Americans [14][15][16] and South Americans, [17][18][19][20] but most frequently among Jews of Ashkenazi origin. 21,22 When inherited from both parents, GBA mutations cause Gaucher disease (GD), a lysosomal storage disorder with 3 clinical types: nonneuropathic (type I), acute neuropathic (type II), and chronic neuropathic (type III).…”

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confidence: 99%

Differential effects of severe vs mild GBA mutations on Parkinson disease

et al. 2015

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“…Mutations in the gene that encodes glucoserebrosidase 1 ( GBA ) have been identified as the most common known genetic risk factor for the development of Parkinson's disease (PD) . Association studies have demonstrated a high incidence of GBA mutations in PD patients, particularly those with early disease onset . PD patients are approximately 6 times more likely to carry GBA mutations than healthy controls.…”

mentioning

confidence: 99%

“…1 Association studies have demonstrated a high incidence of GBA mutations in PD patients, particularly those with early disease onset. [2][3][4] PD patients are approximately 6 times more likely to carry GBA mutations than healthy controls.…”

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confidence: 99%