title: Motor and nonmotor heterogeneity of LRRK2-related and idiopathic Parkinson's disease.
abstract: Parkinson's disease (PD) associated with LRRK2 mutations has been described as similar to idiopathic PD with minor clinical differences. No study has compared the clinical features of LRRK2-associated PD due to different mutations. The objective of this study was to compare LRRK2-associated PD due to G2019S and G2385R mutations and to compare each to idiopathic PD.
  
  
  
  Sites within the international LRRK2 Cohort Consortium undertook family-based, community-based, or clinic-based studies to gather clinical data on manifesting carriers and patients with idiopathic PD.
  
  
  
  Five hundred sixteen PD patients with the G2019S mutation, 199 with the G2385R mutation, and 790 patients with idiopathic PD were included in the data set. Adjusted for age, sex, disease duration, and levodopa-equivalent daily dose, mean MDS-UPDRS part II or III scores and the frequency of motor fluctuations were higher in the G2385R mutation carriers than in either the G2019S mutation carriers or idiopathic PD patients. G2019S mutation carriers had significantly lower UPDRS part III scores than idiopathic PD patients. Both G2019S and G2385R mutation carriers had a higher proportion of the postural instability gait disorder phenotype compared with idiopathic PD patients. LRRK2 G2019S PD patients had better UPSIT scores and lower Geriatric Depression Scale scores than idiopathic PD patients in adjusted analyses.
  
  
  
  G2385R and G2019S PD appear to have motor differences that may be explained by contrasting local treatment or measurement practices or differences in the biology of the disease. Longitudinal studies should evaluate whether progression is faster in G2385R mutation carriers compared with G2019S PD or idiopathic PD. © 2016 International Parkinson and Movement Disorder Society.
authors.affiliation: Toronto Western Hospital Morton and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson's Disease, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Connie
authors.initials: C
authors.lastname: Marras
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, New York, USA.
authors.forename: Roy N
authors.initials: RN
authors.lastname: Alcalay
authors.affiliation: Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USA.
authors.forename: Chelsea
authors.initials: C
authors.lastname: Caspell-Garcia
authors.affiliation: Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Coffey
authors.affiliation: Departments of Neurology and Neurobiology, Xuanwu Hospital of Capital Medical University, China.
authors.forename: Piu
authors.initials: P
authors.lastname: Chan
authors.affiliation: Parkinson's Disease Research, Education and Clinical Center, Michael J. Crescenz VA Medical Center and Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Duda
authors.affiliation: The Michael J. Fox Foundation for Parkinson's Research, New York, New York, USA.
authors.forename: Maurizio F
authors.initials: MF
authors.lastname: Facheris
authors.affiliation: Laboratory of Neurodegenerative Disorders, Department of Neurology, Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, and the Centre for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors.forename: Rubén
authors.initials: R
authors.lastname: Fernández-Santiago
authors.affiliation: Department of Neurology (Movement Disorders Unit), Hospital Universitario Donostia. Biodonostia Research Institute, Neurosciences area. San Sebastián, Guipúzcoa, Spain, and CIBERNED, Carlos III Health Institute, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Ruíz-Martínez
authors.affiliation: Toronto Western Hospital Morton and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson's Disease, University of Toronto, Toronto, Ontario, Canada.|Parkinson's Disease and Movement Disorder Centre, Division of Neurology, Department of Medicine, The Ottawa Hospital, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Tiago
authors.initials: T
authors.lastname: Mestre
authors.affiliation: Department of Neurology, Mount Sinai Beth Israel Medical Center and Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Saunders-Pullman
authors.affiliation: Parkinson's Disease and Movement Disorders Unit, Neurology Service, Hospital Clinic de Barcelona, Universitat de Barcelona, Institutd'InvestigacionsBiomediquesAugust Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Claustre
authors.initials: C
authors.lastname: Pont-Sunyer
authors.affiliation: Parkinson's Disease and Movement Disorders Unit, Neurology Service, Hospital Clinic de Barcelona, Universitat de Barcelona, Institutd'InvestigacionsBiomediquesAugust Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tolosa
authors.affiliation: Department of Neurology, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Bjorg
authors.initials: B
authors.lastname: Waro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000145:classification / Q000235:genetics / Q000503:physiopathology; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
keywords: LRRK2; Parkinson's disease