title: Motor phenotype of LRRK2-associated Parkinson's disease: a Tunisian longitudinal study.
abstract: Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) were found to be a significant cause of late-onset autosomal dominant forms of Parkinson's disease (PD). To determine the motor characteristics of LRRK2-related disease, we conducted a longitudinal study of 58 G2019S LRRK2-associated PD patients and compared them with genetically undefined (GU) PD patients. Fifty-eight patients diagnosed with PD-related LRRK2 G2019S mutation were included in the study and compared with 54 sporadic PD patients with negative tests for LRRK2 G2019S, PINK1, SNCA, PRKN, and DJ1 mutations. Patients were assessed at baseline and after a follow-up period of 6 years. The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), the Hoehn and Yahr, and the Schwab and England scores were determined. Logistic regression was used to examine associations of G2019S mutation status with motor phenotype and rate of motor decline. The LRRK2-associated PD patients had a mean age of onset of 56.25 ± 12.05 years and in most cases (58.6%) a postural instability gait difficulty (PIGD) phenotype. The mean annual decline in the MDS-UDRS III motor score and the Hoehn and Yahr staging was of 1.3% and 2%, respectively. The PIGD phenotype predicted a more rapid progression of motor impairment. The PD motor phenotype and motor scores were similar in the LRRK2-associated PD group and in the GU PD group, with no significant differences in the progression rate of motor impairment. Motor phenotype seems to be similar in LRRK2-related PD and idiopathic PD.
authors.affiliation: Neurology Department, National Institute Mongi Ben Hmida of Neurology, Faculty of Medicine of Tunis, University Tunis El Manar, Tunis, Tunisia.
authors.forename: Fatma
authors.initials: F
authors.lastname: Nabli
authors.forename: Samia
authors.initials: S
authors.lastname: Ben Sassi
authors.forename: Rim
authors.initials: R
authors.lastname: Amouri
authors.forename: John E
authors.initials: JE
authors.lastname: Duda
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Farrer
authors.forename: Fayçal
authors.initials: F
authors.lastname: Hentati
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005684:Gait / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics*; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D014416:Tunisia
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases
keywords: G2019S mutation; LRRK2 gene; PARK8; Parkinson's disease; longitudinal study