Lrrk2 R1441C parkinsonism is clinically similar to sporadic Parkinson disease

K. Haugarvoll, Rosa V Rademakers, J. M. Kachergus, K. Nuytemans, Owen A Ross, J. M. Gibson, E. K. Tan, C. Gaig, E. Tolosa, S. Goldwurm, M. Guidi, G. Riboldazzi, L. Brown, U. Walter, R. Benecke, D. Berg, T. Gasser, J. Theuns, P. Pals, P. CrasP. Paul De Deyn, S. Engelborghs, B. Pickut, R. J. Uitti, T. Foroud, W. C. Nichols, J. Hagenah, C. Klein, A. Samii, C. P. Zabetian, V. Bonifati, C. Van Broeckhoven, M. J. Farrer, Zbigniew K Wszolek

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1456-1460
Number of pages5
JournalNeurology
Volume70
Issue number16 PART 2
DOIs
StatePublished - Apr 2008

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Parkinsonian Disorders
Parkinson Disease
Age of Onset
Leucine
Mutation
Phosphotransferases
Kaplan-Meier Estimate
Mutagenesis
Haplotypes
Incidence

ASJC Scopus subject areas

  • Neuroscience(all)

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Lrrk2 R1441C parkinsonism is clinically similar to sporadic Parkinson disease. / Haugarvoll, K.; Rademakers, Rosa V; Kachergus, J. M.; Nuytemans, K.; Ross, Owen A; Gibson, J. M.; Tan, E. K.; Gaig, C.; Tolosa, E.; Goldwurm, S.; Guidi, M.; Riboldazzi, G.; Brown, L.; Walter, U.; Benecke, R.; Berg, D.; Gasser, T.; Theuns, J.; Pals, P.; Cras, P.; De Deyn, P. Paul; Engelborghs, S.; Pickut, B.; Uitti, R. J.; Foroud, T.; Nichols, W. C.; Hagenah, J.; Klein, C.; Samii, A.; Zabetian, C. P.; Bonifati, V.; Van Broeckhoven, C.; Farrer, M. J.; Wszolek, Zbigniew K.

In: Neurology, Vol. 70, No. 16 PART 2, 04.2008, p. 1456-1460.

Research output: Contribution to journalArticle

Haugarvoll, K, Rademakers, RV, Kachergus, JM, Nuytemans, K, Ross, OA, Gibson, JM, Tan, EK, Gaig, C, Tolosa, E, Goldwurm, S, Guidi, M, Riboldazzi, G, Brown, L, Walter, U, Benecke, R, Berg, D, Gasser, T, Theuns, J, Pals, P, Cras, P, De Deyn, PP, Engelborghs, S, Pickut, B, Uitti, RJ, Foroud, T, Nichols, WC, Hagenah, J, Klein, C, Samii, A, Zabetian, CP, Bonifati, V, Van Broeckhoven, C, Farrer, MJ & Wszolek, ZK 2008, 'Lrrk2 R1441C parkinsonism is clinically similar to sporadic Parkinson disease', Neurology, vol. 70, no. 16 PART 2, pp. 1456-1460. https://doi.org/10.1212/01.wnl.0000304044.22253.03
Haugarvoll, K. ; Rademakers, Rosa V ; Kachergus, J. M. ; Nuytemans, K. ; Ross, Owen A ; Gibson, J. M. ; Tan, E. K. ; Gaig, C. ; Tolosa, E. ; Goldwurm, S. ; Guidi, M. ; Riboldazzi, G. ; Brown, L. ; Walter, U. ; Benecke, R. ; Berg, D. ; Gasser, T. ; Theuns, J. ; Pals, P. ; Cras, P. ; De Deyn, P. Paul ; Engelborghs, S. ; Pickut, B. ; Uitti, R. J. ; Foroud, T. ; Nichols, W. C. ; Hagenah, J. ; Klein, C. ; Samii, A. ; Zabetian, C. P. ; Bonifati, V. ; Van Broeckhoven, C. ; Farrer, M. J. ; Wszolek, Zbigniew K. / Lrrk2 R1441C parkinsonism is clinically similar to sporadic Parkinson disease. In: Neurology. 2008 ; Vol. 70, No. 16 PART 2. pp. 1456-1460.
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abstract = "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.",
author = "K. Haugarvoll and Rademakers, {Rosa V} and Kachergus, {J. M.} and K. Nuytemans and Ross, {Owen A} and Gibson, {J. M.} and Tan, {E. K.} and C. Gaig and E. Tolosa and S. Goldwurm and M. Guidi and G. Riboldazzi and L. Brown and U. Walter and R. Benecke and D. Berg and T. Gasser and J. Theuns and P. Pals and P. Cras and {De Deyn}, {P. Paul} and S. Engelborghs and B. Pickut and Uitti, {R. J.} and T. Foroud and Nichols, {W. C.} and J. Hagenah and C. Klein and A. Samii and Zabetian, {C. P.} and V. Bonifati and {Van Broeckhoven}, C. and Farrer, {M. J.} and Wszolek, {Zbigniew K}",
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T1 - Lrrk2 R1441C parkinsonism is clinically similar to sporadic Parkinson disease

AU - Haugarvoll, K.

AU - Rademakers, Rosa V

AU - Kachergus, J. M.

AU - Nuytemans, K.

AU - Ross, Owen A

AU - Gibson, J. M.

AU - Tan, E. K.

AU - Gaig, C.

AU - Tolosa, E.

AU - Goldwurm, S.

AU - Guidi, M.

AU - Riboldazzi, G.

AU - Brown, L.

AU - Walter, U.

AU - Benecke, R.

AU - Berg, D.

AU - Gasser, T.

AU - Theuns, J.

AU - Pals, P.

AU - Cras, P.

AU - De Deyn, P. Paul

AU - Engelborghs, S.

AU - Pickut, B.

AU - Uitti, R. J.

AU - Foroud, T.

AU - Nichols, W. C.

AU - Hagenah, J.

AU - Klein, C.

AU - Samii, A.

AU - Zabetian, C. P.

AU - Bonifati, V.

AU - Van Broeckhoven, C.

AU - Farrer, M. J.

AU - Wszolek, Zbigniew K

PY - 2008/4

Y1 - 2008/4

N2 - 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.

AB - 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.

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