Dataset Information

Gait asymmetry in glucocerebrosidase mutation carriers with Parkinson's disease.

ABSTRACT: Background: GBA mutation carriers with PD (PD-GBA) are at higher risk of cognitive decline, but there is limited data regarding whether there are differences in gait dysfunction between GBA mutation and non-mutation carriers with PD.

Objectives/methods: The primary aim of this study was to use quantitative inertial sensor-based gait analysis to compare gait asymmetry in 17 PD-GBA subjects, 17 non-mutation carriers with PD, and 15 healthy control subjects using parameters that had gait laterality and were markers of bradykinesia, in particular arm swing velocity and arm swing range of motion and stride length.

Results: Arm swing velocity was more symmetric in PD-GBA subjects vs. non-mutation carriers in the OFF state (12.5 +/- 8.3 vs. 22.9 +/- 11.8%, respectively, p = 0.018). In the ON-medication state, non-mutation carriers with PD, but not PD-GBA subjects, exhibited arm swing velocity (16.8 +/- 8.6 vs. 22.9 +/- 11.8%, p = 0.006) and arm range of motion (26.7 +/- 16.3 vs. 33.4 +/- 18.6%, p = 0.02) that was more asymmetric compared with the OFF-medication state.

Conclusions: In the OFF medication state, arm swing velocity asymmetry may be a useful parameter in helping to distinguish GBA mutation carriers with PD from non-mutation carriers.

SUBMITTER: Gera A

PROVIDER: S-EPMC6980620 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Gait asymmetry in glucocerebrosidase mutation carriers with Parkinson's disease.

Gera Anjali A O'Keefe Joan A JA Ouyang Bichun B Liu Yuanqing Y Ruehl Samantha S Buder Mark M Joyce Jessica J Purcell Nicolette N Pal Gian G

PloS one 20200124 1

<h4>Background</h4>GBA mutation carriers with PD (PD-GBA) are at higher risk of cognitive decline, but there is limited data regarding whether there are differences in gait dysfunction between GBA mutation and non-mutation carriers with PD.<h4>Objectives/methods</h4>The primary aim of this study was to use quantitative inertial sensor-based gait analysis to compare gait asymmetry in 17 PD-GBA subjects, 17 non-mutation carriers with PD, and 15 healthy control subjects using parameters that had ga ...[more]

PMID: 31978134

Similar Datasets

Project description:GTP cyclohydrolase 1, encoded by the GCH1 gene, is an essential enzyme for dopamine production in nigrostriatal cells. Loss-of-function mutations in GCH1 result in severe reduction of dopamine synthesis in nigrostriatal cells and are the most common cause of DOPA-responsive dystonia, a rare disease that classically presents in childhood with generalized dystonia and a dramatic long-lasting response to levodopa. We describe clinical, genetic and nigrostriatal dopaminergic imaging ([(123)I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) tropane single photon computed tomography) findings of four unrelated pedigrees with DOPA-responsive dystonia in which pathogenic GCH1 variants were identified in family members with adult-onset parkinsonism. Dopamine transporter imaging was abnormal in all parkinsonian patients, indicating Parkinson's disease-like nigrostriatal dopaminergic denervation. We subsequently explored the possibility that pathogenic GCH1 variants could contribute to the risk of developing Parkinson's disease, even in the absence of a family history for DOPA-responsive dystonia. The frequency of GCH1 variants was evaluated in whole-exome sequencing data of 1318 cases with Parkinson's disease and 5935 control subjects. Combining cases and controls, we identified a total of 11 different heterozygous GCH1 variants, all at low frequency. This list includes four pathogenic variants previously associated with DOPA-responsive dystonia (Q110X, V204I, K224R and M230I) and seven of undetermined clinical relevance (Q110E, T112A, A120S, D134G, I154V, R198Q and G217V). The frequency of GCH1 variants was significantly higher (Fisher's exact test P-value 0.0001) in cases (10/1318 = 0.75%) than in controls (6/5935 = 0.1%; odds ratio 7.5; 95% confidence interval 2.4-25.3). Our results show that rare GCH1 variants are associated with an increased risk for Parkinson's disease. These findings expand the clinical and biological relevance of GTP cycloydrolase 1 deficiency, suggesting that it not only leads to biochemical striatal dopamine depletion and DOPA-responsive dystonia, but also predisposes to nigrostriatal cell loss. Further insight into GCH1-associated pathogenetic mechanisms will shed light on the role of dopamine metabolism in nigral degeneration and Parkinson's disease.

Dataset Information

Gait asymmetry in glucocerebrosidase mutation carriers with Parkinson's disease.

Publications

Gait asymmetry in glucocerebrosidase mutation carriers with Parkinson's disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets