Lrrk2 R1441C parkinsonism is clinically similar to sporadic Parkinson disease

被引：117

作者：

Haugarvoll, K. ^{[1
,2
,3
]}

Rademakers, R. ^{[1
,2
,4
,5
,6
]}

Kachergus, J. M. ^{[1
,2
]}

Nuytemans, K. ^{[4
,5
,6
]}

Ross, O. A. ^{[1
,2
]}

Gibson, J. M. ^{[7
]}

Tan, E. -K. ^{[8
]}

Gaig, C. ^{[9
,10
]}

Tolosa, E. ^{[9
,10
]}

Goldwurm, S. ^{[11
]}

Guidi, M. ^{[12
]}

Riboldazzi, G. ^{[13
]}

Brown, L. ^{[1
,2
]}

Walter, U. ^{[14
]}

Benecke, R. ^{[14
]}

Berg, D. ^{[15
]}

Gasser, T. ^{[15
]}

Theuns, J. ^{[4
,5
,6
]}

Pals, P. ^{[6
,16
,17
]}

Cras, P. ^{[6
,16
,17
]}

De Deyn, P. Paul ^{[6
,18
,19
]}

Engelborghs, S. ^{[6
,18
,19
]}

Pickut, B. ^{[19
]}

Uitti, R. J. ^{[1
,2
]}

Foroud, T. ^{[20
]}

Nichols, W. C. ^{[21
,22
]}

Hagenah, J. ^{[23
]}

Klein, C. ^{[23
]}

Samii, A. ^{[24
]}

Zabetian, C. P. ^{[24
]}

Bonifati, V. ^{[25
]}

Van Broeckhoven, C. ^{[4
,5
,6
]}

Farrer, M. J. ^{[1
,2
]}

Wszolek, Z. K. ^{[1
,2
]}

机构：

[1] Mayo Clin, Coll Med, Dept Neurol, Jacksonville, FL 32224 USA

[2] Mayo Clin, Coll Med, Dept Neurosci, Jacksonville, FL 32224 USA

[3] NTNU Norwegian Univ Sci & Technol, Dept Neurosci, Trondheim, Norway

[4] Inst Born Bunge, Neurodegenerat Brain Dis Grp, Antwerp, Belgium

[5] Inst Born Bunge, Dept Mol Genet, VIB, Neurogenet Lab, Antwerp, Belgium

[6] Univ Antwerp, B-2020 Antwerp, Belgium

[7] Royal Victoria Hosp, Dept Neurol, Belfast BT12 6BA, Antrim, North Ireland

[8] Singapore Gen Hosp, Singapore 0316, Singapore

[9] Univ Barcelona, Parkinsons Dis & Movement Disorders Unit, E-08007 Barcelona, Spain

[10] Univ Barcelona, Hosp Clin Barcelona, Inst Invest Biomed August Pi & Sunyer, Ctr Invest Biomed Red Enfermedades Neurodegenerat, E-08007 Barcelona, Spain

[11] Ist Clin Perfezionamento, Parkinson Inst, Milan, Italy

[12] INRCA Inst, Div Neurol, Ancona, Italy

[13] Univ Insubria, Dept Neurol, Varese, Italy

[14] Univ Rostock, Dept Neurol, D-2500 Rostock 1, Germany

[15] Hertie Inst Clin Brain Res, Tubingen, Germany

[16] Univ Antwerp Hosp, Div Neurol, Antwerp, Belgium

[17] Inst Born Bunge, Neurobiol Lab, Antwerp, Belgium

[18] Inst Born Bunge, Lab Neurochem & Behav, Antwerp, Belgium

[19] ZNA Middelheim Antwerp, Div Neurol, Antwerp, Belgium

[20] Indiana Univ, Sch Med, Indianapolis, IN 46204 USA

[21] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA

[22] Univ Cincinnati, Coll Med, Cincinnati, OH 45221 USA

[23] Uni Lubeck, Dept Neurol & Human Genet, Lubeck, Germany

[24] Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA

[25] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands

来源：

NEUROLOGY | 2008年 / 70卷 / 16期

关键词：

D O I：

10.1212/01.wnl.0000304044.22253.03

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Objective: Leucine-rich repeat kinase 2 (LRRK2) mutations are the most common cause of Parkinson disease (PD). Several dominantly inherited pathogenic substitutions have been identified in different domains of the Lrrk2 protein. Herein, we characterize the clinical and genetic features associated with Lrrk2 p. R1441C. Methods: We identified 33 affected and 15 unaffected LRRK2 c. 4321C>T (p. R1441C) mutation carriers through an international consortium originating from three continents. The age-specific cumulative incidence of PD was calculated by Kaplan-Meier analysis. Results: The clinical presentation of Lrrk2 p.R1441C carriers was similar to sporadic PD and Lrrk2 p.G2019S parkinsonism. The mean age at onset for parkinsonism was 60 years, range 30-79 years; fewer than 20% of the patients had symptoms before the age 50 years, while by 75 years >90% of them had developed symptoms. Haplotype analysis suggests four independent founders for the p. R1441C mutation. Conclusions: The distribution in age at onset and clinical features in Lrrk2 p.R1441C patients are similar to idiopathic and Lrrk2 p.G2019S parkinsonism. Several independent founders of the p.R1441C substitution suggest this site is prone to recurrent mutagenesis.

引用

页码：1456 / 1460

页数：5

共 30 条

[1] Comprehensive analysis of the LRRK2 gene in sixty families with Parkinson's disease
Di Fonzo, A
Tassorelli, C
De Mari, M
Chien, HF
Ferreira, J
Rohé, CF
Riboldazzi, G
Antonini, A
Albani, G
Mauro, A
Marconi, R
Abbruzzese, G
Lopiano, L
Fincati, E
Guidi, M
Marini, P
Stocchi, F
Onofrj, M
Toni, V
Tinazzi, M
Fabbrini, G
Lamberti, P
Vanacore, N
Meco, G
Leitner, P
Uitti, RJ
Wszolek, ZK
Gasser, T
Simons, EJ
Breedveld, GJ
Goldwurm, S
Pezzoli, G
Sampaio, C
Barbosa, E
Martignoni, E
Oostra, BA
Bonifati, V
[J]. EUROPEAN JOURNAL OF HUMAN GENETICS, 2006, 14 (03) : 322 - 331
[2] A common missense variant in the LRRK2 gene, Gly2385Arg, associated with Parkinson's disease risk in Taiwan
Di Fonzo, Alessio
Wu-Chou, Yah-Huei
Lu, Chin-Song
van Doeselaar, Marina
Simons, Erik J.
Rohe, Christan F.
Chang, Hsiu-Chen
Chen, Rou-Shayn
Weng, Yi-Hsin
Vanacore, Nicola
Breedveld, Guido J.
Oostra, Ben A.
Bonifati, Vincenzo
[J]. NEUROGENETICS, 2006, 7 (03) : 133 - 138
[3] Fahn S, 1987, Recent Dev. Park. Dis, P153
[4] Lrrk2 G2385R is an ancestral risk factor for Parkinson's disease in Asia
Farrer, Matthew J.
Stone, Jeremy T.
Lin, Chin-Hsien
Dachsel, Justus C.
Hulihan, Mary M.
Haugarvoll, Kristoffer
Ross, Owen A.
Wu, Ruey-Meei
[J]. PARKINSONISM & RELATED DISORDERS, 2007, 13 (02) : 89 - 92
[5] Leucine-Rich Repeat kinase 2 G238SR variant is a risk factor for Parkinson disease in Asian population
Funayama, Manabu
Li, Yuanzhe
Tomiyama, Hiroyuki
Yoshino, Hiroyo
Imamichi, Yoko
Yamamoto, Mitsutoshi
Murata, Miho
Toda, Tatsushi
Mizuno, Yoshikuni
Hattori, Nobutaka
[J]. NEUROREPORT, 2007, 18 (03) : 273 - 275
[6] A common genetic factor for Parkinson disease in ethnic Chinese population in Taiwan
Fung, Hon-Chung
Chen, Chiung-Mei
Hardy, John
Singleton, Andrew B.
Wu, Yih-Ru
[J]. BMC NEUROLOGY, 2006, 6 (1)
[7] LRRK2 mutations in Spanish patients with Parkinson disease -: Frequency, clinical features, and incomplete penetrance
Gaig, C
Ezquerra, M
Marti, MJ
Muñoz, E
Valldeoriola, F
Tolosa, E
[J]. ARCHIVES OF NEUROLOGY, 2006, 63 (03) : 377 - 382
[8] Diagnostic criteria for Parkinson disease
Gelb, DJ
Oliver, E
Gilman, S
[J]. ARCHIVES OF NEUROLOGY, 1999, 56 (01) : 33 - 39
[9] The G6055A (G2019S) mutation in LRRK2 is frequent in both early and late onset Parkinson's disease and originates from a common ancestor -: art. no. e65
Goldwurm, S
Di Fonzo, A
Simons, EJ
Rohé, CF
Zini, M
Canesi, M
Tesei, S
Zecchinelli, A
Antonini, A
Mariani, C
Meucci, N
Sacilotto, G
Sironi, F
Salani, G
Ferreira, J
Chien, HF
Fabrizio, E
Vanacore, N
Dalla Libera, A
Stocchi, F
Diroma, C
Lamberti, P
Sampaio, C
Meco, G
Barbosa, E
Bertoli-Avella, AM
Breedveld, GJ
Oostra, BA
Pezzoli, G
Bonifati, V
[J]. JOURNAL OF MEDICAL GENETICS, 2005, 42 (11) : e65
[10] Global distribution and reduced penetrance: Lrrk2 R1441C in an Irish Parkinson's disease kindred
Gosal, David
Lynch, Timothy
Ross, Owen A.
Haugarvoll, Kristoffer
Farrer, Matthew J.
Gibson, J. Mark
[J]. MOVEMENT DISORDERS, 2007, 22 (02) : 291 - 292

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