Early-onset parkinsonism associated with PINK1 mutations
Frequency, genotypes, and phenotypes
Citation Manager Formats
Make Comment
See Comments
![Loading Loading](https://n.neurology.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif)
This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
Abstract
Objective: To assess the prevalence, nature, and associated phenotypes of PINK1 gene mutations in a large series of patients with early-onset (<50 years) parkinsonism.
Methods: The authors studied 134 patients (116 sporadic and 18 familial; 77% Italian) and 90 Italian controls. The whole PINK1 coding region was sequenced from genomic DNA; cDNA was analyzed in selected cases.
Results: Homozygous pathogenic mutations were identified in 4 of 90 Italian sporadic cases, including the novel Gln456Stop mutation; single heterozygous truncating or missense mutations were found in another 4 Italian sporadic cases, including two novel mutations, Pro196Leu and Gln456Stop. Pathogenic mutations were not identified in the familial cases. Novel (Gln115Leu) and known polymorphisms were identified with similar frequency in cases and controls. In cases carrying single heterozygous mutation, cDNA analysis detected no additional mutations, and revealed a major pathogenic effect at mRNA level for the mutant C1366T/Gln456Stop allele. All patients with homozygous mutations had very early disease onset, slow progression, and excellent response to l-dopa, including, in some, symmetric onset, dystonia at onset, and sleep benefit, resembling parkin-related disease. Phenotype in patients with single heterozygous mutation was similar, but onset was later.
Conclusions: PINK1 homozygous mutations are a relevant cause of disease among Italian sporadic patients with early-onset parkinsonism. The role of mutations found in single heterozygous state is difficult to interpret. Our study suggests that, at least in some patients, these mutations are disease causing, in combination with additional, still unknown factors.
AAN Members
We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page.
AAN Non-Member Subscribers
Purchase access
For assistance, please contact:
AAN Members (800) 879-1960 or (612) 928-6000 (International)
Non-AAN Member subscribers (800) 638-3030 or (301) 223-2300 option 3, select 1 (international)
Sign Up
Information on how to subscribe to Neurology and Neurology: Clinical Practice can be found here
Purchase
Individual access to articles is available through the Add to Cart option on the article page. Access for 1 day (from the computer you are currently using) is US$ 39.00. Pay-per-view content is for the use of the payee only, and content may not be further distributed by print or electronic means. The payee may view, download, and/or print the article for his/her personal, scholarly, research, and educational use. Distributing copies (electronic or otherwise) of the article is not allowed.
Letters: Rapid online correspondence
- Biologic effect of a PINK1 mutation: mRNA levels of the c.1366C>T (Gln456Stop) change
- Christine Klein, MD, University of Luebeck Neurology, Ratzeburger Allee 160, 23538 Lübeckchristine.klein@neuro.uni-luebeck.de
- Anne Grünewald (Department of Neurology), Katja Hedrich (Department of Neurology and Human Genetics, University of Lübeck
Submitted November 08, 2005 - Reply to authors
- Vincenzo Bonifati, Department of Clinical Genetics, Erasmus MC Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlandsv.bonifati@erasmusmc.nl
- Christan F. Rohé, Guido J. Breedveld, and Ben A. Oostra.
Submitted November 08, 2005
REQUIREMENTS
You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.
You May Also be Interested in
Dr. Fabricio Ferreira de Oliveira and Dr. Alan Cronemberger Andrade
► Watch
Topics Discussed
Alert Me
Recommended articles
-
Articles
ATP13A2 missense mutations in juvenile parkinsonism and young onset Parkinson diseaseA. Di Fonzo, H. F. Chien, M. Socal et al.Neurology, May 07, 2007 -
Articles
A multidisciplinary study of patients with early-onset PD with and without parkin mutationsE. Lohmann, S. Thobois, S. Lesage et al.Neurology, November 05, 2008 -
Brief Communications
Clinicogenetic study of PINK1 mutations in autosomal recessive early-onset parkinsonismY. Li, H. Tomiyama, K. Sato et al.Neurology, June 13, 2005 -
Articles
Progression of subtle motor signs in PINK1 mutation carriers with mild dopaminergic deficitC. Eggers, A. Schmidt, J. Hagenah et al.Neurology, May 31, 2010