title: Comparative study of Parkinson's disease and leucine-rich repeat kinase 2 p.G2019S parkinsonism.
abstract: Parkinson disease is a progressive neurodegenerative disease for which leucine-rich repeat kinase 2 (LRRK2 carriers) p.G2019S confers substantial genotypic and population attributable risk. With informed consent, we have recruited clinical data from 778 patients from Tunisia (of which 266 have LRRK2 parkinsonism) and 580 unaffected subjects. Motor, autonomic, and cognitive assessments in idiopathic Parkinson disease and LRRK2 patients were compared with regression models. The age-associated cumulative incidence of LRRK2 parkinsonism was also estimated using case-control and family-based designs. LRRK2 parkinsonism patients had slightly less gastrointestinal dysfunction and rapid eye movement sleep disorder. Overall, disease penetrance in LRRK2 carriers was 80% by 70 years but women become affected a median 5 years younger than men. Idiopathic Parkinson disease patients with younger age at diagnosis have slower disease progression. However, age at diagnoses does not predict progression in LRRK2 parkinsonism. LRRK2 p.G2019S mutation is a useful aid to diagnosis and modifiers of disease in LRRK2 parkinsonism may aid in developing therapeutic targets.
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada. Electronic address: jtrinh@can.ubc.ca.
authors.forename: Joanne
authors.initials: J
authors.lastname: Trinh
authors.affiliation: Mongi Ben Hamida National Institute of neurology, Tunis, Tunisia.
authors.forename: Rim
authors.initials: R
authors.lastname: Amouri
authors.affiliation: Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Duda
authors.affiliation: Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: James F
authors.initials: JF
authors.lastname: Morley
authors.affiliation: PRN, Basingstoke, Hants, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Read
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Alan
authors.initials: A
authors.lastname: Donald
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Carles
authors.initials: C
authors.lastname: Vilariño-Güell
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Christina
authors.initials: C
authors.lastname: Thompson
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Chelsea
authors.initials: C
authors.lastname: Szu Tu
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Emil K
authors.initials: EK
authors.lastname: Gustavsson
authors.affiliation: Mongi Ben Hamida National Institute of neurology, Tunis, Tunisia.
authors.forename: Samia
authors.initials: S
authors.lastname: Ben Sassi
authors.affiliation: Mongi Ben Hamida National Institute of neurology, Tunis, Tunisia.
authors.forename: Emna
authors.initials: E
authors.lastname: Hentati
authors.affiliation: Mongi Ben Hamida National Institute of neurology, Tunis, Tunisia.
authors.forename: Mourad
authors.initials: M
authors.lastname: Zouari
authors.affiliation: Mongi Ben Hamida National Institute of neurology, Tunis, Tunisia.
authors.forename: Emna
authors.initials: E
authors.lastname: Farhat
authors.affiliation: Mongi Ben Hamida National Institute of neurology, Tunis, Tunisia.
authors.forename: Fatma
authors.initials: F
authors.lastname: Nabli
authors.affiliation: Mongi Ben Hamida National Institute of neurology, Tunis, Tunisia.
authors.forename: Faycel
authors.initials: F
authors.lastname: Hentati
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Farrer
mesh_terms: D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D016022:Case-Control Studies; D003071:Cognition; D018450:Disease Progression; D005260:Female; D006801:Humans; D015994:Incidence; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009043:Motor Activity; D009154:Mutation; D010300:Parkinson Disease / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012044:Regression Analysis; D012306:Risk; D012737:Sex Factors
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases
keywords: Genetics; LRRK2 parkinsonism; Parkinson disease; Penetrance