Skip Navigation


Brain Advance Access originally published online on January 9, 2006
Brain 2006 129(3):686-694; doi:10.1093/brain/awl005
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
129/3/686    most recent
awl005v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (21)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Ibáñez, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ibáñez, P.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published by Oxford University Press on behalf of the Guarantors of Brain. For Permissions, please email: journals.permissions@oxfordjournals.org

Mutational analysis of the PINK1 gene in early-onset parkinsonism in Europe and North Africa

Pablo Ibáñez1, Suzanne Lesage1, Ebba Lohmann1,3, Stéphane Thobois5, Giuseppe De Michele7, Michel Borg6, Yves Agid1,3,4, Alexandra Dürr1,2,3, Alexis Brice1,2,3,4 and the French Parkinson's Disease Genetics Study Group

1 INSERM U679 (former U289), Neurologie et Thérapeutique Expérimentale, CHU Pitié-Salpêtrière, 2 Département de Génétique, Cytogénétique et Embryologie, CHU Pitié-Salpêtrière, 3 Fédération de Neurologie, CHU Pitié-Salpêtrière, 4 UFR, CHU Pitié-Salpêtrière, Paris, 5 Service de Neurologie C, Hôpital Neurologique de Lyon, Lyon, 6 Service de Neurologie, CHU de Nice, Nice, France and 7 Department of Neurological Sciences, Federico II University, Naples, Italy

Correspondence to: Alexis Brice, INSERM U679, Hôpital de la Salpêtrière, 47, Boulevard de l'Hôpital, 75651 Paris cedex 13, France E-mail: brice{at}ccr.jussieu.fr

Parkinson's disease is a frequent disorder caused primarily by the loss of dopaminergic neurons of the substantia nigra. Mutations in the PTEN-induced kinase (PINK1) gene, in addition to those in parkin and DJ-1, have been found in families with recessive early-onset Parkinson's disease. We screened for parkin and PINK1 mutations in a panel of 177 autosomal recessive Parkinson's disease families with ages at onset ≤60 years, mostly from Europe. In 7 unrelated families, we identified 10 pathogenic PINK1 mutations (5 missense, 2 nonsense and 3 frameshift deletion mutations), 8 of which were novel. All the mutations were in the homozygous or compound heterozygous states. Interestingly, pseudo-dominant inheritance was observed in a family with two different mutations. The clinical characteristics of 12 PINK1 patients and 114 parkin patients were similar, even for signs such as dystonia at onset and increased reflexes, which were thought to be specific to parkin. In contrast, onset in patients with PINK1 mutations was earlier and increased reflexes were found more frequently than in patients without PINK1 or parkin mutations. These results suggest that PINK1 is the second most frequent causative gene in early-onset Parkinson's disease with a slowly progressive phenotype, indistinguishable from early-onset patients with parkin mutations.

Key Words: early-onset parkinsonism; PINK1; parkin; mutation

Abbreviations: EOP = early-onset parkinsonism; PINK1 = PTEN-induced putative kinase; UPDRS = Unified Parkinson's Disease Rating Scale

Received September 9, 2005. Revised December 8, 2005. Accepted December 9, 2005.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Arch NeurolHome page
R. Kumazawa, H. Tomiyama, Y. Li, Y. Imamichi, M. Funayama, H. Yoshino, F. Yokochi, T. Fukusako, Y. Takehisa, K. Kashihara, et al.
Mutation Analysis of the PINK1 Gene in 391 Patients With Parkinson Disease
Arch Neurol, June 1, 2008; 65(6): 802 - 808.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
A. Weihofen, B. Ostaszewski, Y. Minami, and D. J. Selkoe
Pink1 Parkinson mutations, the Cdc37/Hsp90 chaperones and Parkin all influence the maturation or subcellular distribution of Pink1
Hum. Mol. Genet., February 14, 2008; 17(4): 602 - 616.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
S Lesage, E Lohmann, F Tison, F Durif, A Durr, A Brice, and for the French Parkinson's Disease Genetics Study
Rare heterozygous parkin variants in French early-onset Parkinson disease patients and controls
J. Med. Genet., January 1, 2008; 45(1): 43 - 46.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
T. Kitada, A. Pisani, D. R. Porter, H. Yamaguchi, A. Tscherter, G. Martella, P. Bonsi, C. Zhang, E. N. Pothos, and J. Shen
From the Cover: Impaired dopamine release and synaptic plasticity in the striatum of PINK1-deficient mice
PNAS, July 3, 2007; 104(27): 11441 - 11446.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurol. Neurosurg. PsychiatryHome page
M Toft, R Myhre, L Pielsticker, L R White, J O Aasly, and M J Farrer
PINK1 mutation heterozygosity and the risk of Parkinson's disease
J. Neurol. Neurosurg. Psychiatry, January 1, 2007; 78(1): 82 - 84.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
C. H. Sim, D. S. S. Lio, S. S. Mok, C. L. Masters, A. F. Hill, J. G. Culvenor, and H.-C. Cheng
C-terminal truncation and Parkinson's disease-associated mutations down-regulate the protein serine/threonine kinase activity of PTEN-induced kinase-1
Hum. Mol. Genet., November 1, 2006; 15(21): 3251 - 3262.
[Abstract] [Full Text] [PDF]

Home page
 Arch NeurolHome page
A.-L. Leutenegger, M. A. M. Salih, P. Ibanez, M. M. Mukhtar, S. Lesage, A. Arabi, E. Lohmann, A. Durr, A. E. M. Ahmed, and A. Brice
Juvenile-Onset Parkinsonism as a Result of the First Mutation in the Adenosine Triphosphate Orientation Domain of PINK1.
Arch Neurol, September 1, 2006; 63(9): 1257 - 1261.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.