title: Fall risk and gait in Parkinson's disease: the role of the LRRK2 G2019S mutation.
abstract: Patients with Parkinson's disease (PD) who carry the G2019S mutation (a glycine to serine substitution at amino acid 2019) in the leucine-rich repeat kinase 2 (LRRK2) gene are generally believed to be clinically indistinguishable from patients with sporadic PD. There are, however, conflicting reports on the relationship between the mutation and the motor phenotype. We quantitatively compared gait and mobility in patients with PD carriers of the G2019S mutation to non-carrier patients with PD to better understand the genotype-phenotype relationship. Fifty patients with PD carriers of the G2019S LRRK2 mutation and 50 age, disease duration, and disease severity matched PD non-carriers were studied. An accelerometer quantified gait under three walking conditions: usual-walking, dual-tasking, and fast-walking. The Unified Parkinson's Disease Rating Scale classified patients into PD sub-types and the Timed Up and Go quantified mobility and fall risk. In all three walking conditions, gait variability was larger and the walking pattern was less consistent among the PD mutation carriers (P < 0.016). The PD carriers also took longer to complete the Timed Up and Go (P = 0.011) and were more likely to report having fallen in the previous year (P = 0.018). 64% of the PD carriers were classified as belonging to the postural-instability-gait-difficulty (PIGD) sub-type compared to only 17% of the PD non-carriers (P < 0.0001). Among patients with PD, the G2019S mutation in the LRRK2 gene is apparently associated with increased gait variability, an increased fall risk, and the PIGD sub-type. Therapeutic approach specifically designed to delay gait disturbances and falls may be justified in patients who carry the G2019S mutation.
authors.affiliation: Movement Disorders Unit, Department of Neurology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel; School of Health-Related Professions, Ben Gurion University, Beer Sheba, Israel.
authors.forename: Anat
authors.initials: A
authors.lastname: Mirelman
authors.forename: Talia
authors.initials: T
authors.lastname: Heman
authors.forename: Kira
authors.initials: K
authors.lastname: Yasinovsky
authors.forename: Avner
authors.initials: A
authors.lastname: Thaler
authors.forename: Tanya
authors.initials: T
authors.lastname: Gurevich
authors.forename: Karen
authors.initials: K
authors.lastname: Marder
authors.forename: Susan
authors.initials: S
authors.lastname: Bressman
authors.forename: Anat
authors.initials: A
authors.lastname: Bar-Shira
authors.forename: Avi
authors.initials: A
authors.lastname: Orr-Urtreger
authors.forename: Nir
authors.initials: N
authors.lastname: Giladi
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Hausdorff
mesh_terms: D000058:Accidental Falls; D000368:Aged; D005260:Female; D005684:Gait / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype; D004856:Postural Balance / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012306:Risk
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases
keywords: G2019S; LRRK2; Parkinson's disease; falls; gait