TY - JOUR
T1 - A comparative study of Parkinson's disease and leucine-rich repeat kinase 2 p.G2019S parkinsonism
AU - Trinh, Joanne
AU - Amouri, Rim
AU - Duda, John E.
AU - Morley, James F.
AU - Read, Matthew
AU - Donald, Alan
AU - Vilariño-Güell, Carles
AU - Thompson, Christina
AU - Szu Tu, Chelsea
AU - Gustavsson, Emil K.
AU - Ben Sassi, Samia
AU - Hentati, Emna
AU - Zouari, Mourad
AU - Farhat, Emna
AU - Nabli, Fatma
AU - Hentati, Faycel
AU - Farrer, Matthew J.
N1 - Funding Information:
The authors gratefully acknowledge the help and support of the patients and families involved in this study. Research funding was awarded by the Michael J. Fox Foundation and the National Institutes of Health (FH, MJF). The Canada Excellence Research Chairs program, the Cundill Foundation, and Leading Edge Endowment Funds provided by the Province of British Columbia, LifeLabs , and Genome BC help support the Dr Donald Rix BC Leadership Chair (MJF) and fellowship (JT). The authors gratefully acknowledge the work and support of prior studies lead by Rachel Gibson, Lefkos Middleton, and the GlaxoSmithKline program team.
PY - 2014/5
Y1 - 2014/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84893770183&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2013.11.015
DO - 10.1016/j.neurobiolaging.2013.11.015
M3 - Journal articles
C2 - 24355527
AN - SCOPUS:84893770183
SN - 0197-4580
VL - 35
SP - 1125
EP - 1131
JO - Neurobiology of Aging
JF - Neurobiology of Aging
IS - 5
ER -