A comparative study of Parkinson's disease and leucine-rich repeat kinase 2 p.G2019S parkinsonism

Joanne Trinh; Rim Amouri; John E. Duda; James F. Morley; Matthew Read; Alan Donald; Carles Vilariño-Güell; Christina Thompson; Chelsea Szu Tu; Emil K. Gustavsson; Samia Ben Sassi; Emna Hentati; Mourad Zouari; Emna Farhat; Fatma Nabli; Faycel Hentati; Matthew J. Farrer

doi:10.1016/j.neurobiolaging.2013.11.015

A comparative study of Parkinson's disease and leucine-rich repeat kinase 2 p.G2019S parkinsonism

Joanne Trinh^*, Rim Amouri, John E. Duda, James F. Morley, Matthew Read, Alan Donald, Carles Vilariño-Güell, Christina Thompson, Chelsea Szu Tu, Emil K. Gustavsson, Samia Ben Sassi, Emna Hentati, Mourad Zouari, Emna Farhat, Fatma Nabli, Faycel Hentati, Matthew J. Farrer

^*Korrespondierende/r Autor/-in für diese Arbeit

Institut für Neurogenetik

79 Zitate (Scopus)

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.

Originalsprache	Englisch
Zeitschrift	Neurobiology of Aging
Jahrgang	35
Ausgabenummer	5
Seiten (von - bis)	1125-1131
Seitenumfang	7
ISSN	0197-4580
DOIs	https://doi.org/10.1016/j.neurobiolaging.2013.11.015
Publikationsstatus	Veröffentlicht - 05.2014

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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.

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10.1016/j.neurobiolaging.2013.11.015

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Trinh, J., Amouri, R., Duda, J. E., Morley, J. F., Read, M., Donald, A., Vilariño-Güell, C., Thompson, C., Szu Tu, C., Gustavsson, E. K., Ben Sassi, S., Hentati, E., Zouari, M., Farhat, E., Nabli, F., Hentati, F., & Farrer, M. J. (2014). A comparative study of Parkinson's disease and leucine-rich repeat kinase 2 p.G2019S parkinsonism. Neurobiology of Aging, 35(5), 1125-1131. https://doi.org/10.1016/j.neurobiolaging.2013.11.015

@article{b522d01e9ff942029da27cd2f8b6ab28,

title = "A 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.",

author = "Joanne Trinh and Rim Amouri and Duda, \{John E.\} and Morley, \{James F.\} and Matthew Read and Alan Donald and Carles Vilari{\~n}o-G{\"u}ell and Christina Thompson and \{Szu Tu\}, Chelsea and Gustavsson, \{Emil K.\} and \{Ben Sassi\}, Samia and Emna Hentati and Mourad Zouari and Emna Farhat and Fatma Nabli and Faycel Hentati and Farrer, \{Matthew J.\}",

note = "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. ",

year = "2014",

month = may,

doi = "10.1016/j.neurobiolaging.2013.11.015",

language = "English",

volume = "35",

pages = "1125--1131",

journal = "Neurobiology of Aging",

issn = "0197-4580",

publisher = "Elsevier Inc.",

number = "5",

}

Trinh, J, Amouri, R, Duda, JE, Morley, JF, Read, M, Donald, A, Vilariño-Güell, C, Thompson, C, Szu Tu, C, Gustavsson, EK, Ben Sassi, S, Hentati, E, Zouari, M, Farhat, E, Nabli, F, Hentati, F & Farrer, MJ 2014, 'A comparative study of Parkinson's disease and leucine-rich repeat kinase 2 p.G2019S parkinsonism', Neurobiology of Aging, Jg. 35, Nr. 5, S. 1125-1131. https://doi.org/10.1016/j.neurobiolaging.2013.11.015

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 - https://www.scopus.com/pages/publications/84893770183

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 -

A comparative study of Parkinson's disease and leucine-rich repeat kinase 2 p.G2019S parkinsonism

Abstract

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