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: 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.
GLOSSARY: COR = C-terminal of Roc; GTPase = guanosine triphosphatase; LBD = Lewy body disease; PD = Parkinson disease; SNPs = single nucleotide polymorphisms.
Footnotes
-
wszolek.zbigniew{at}mayo.edu
Supplemental data at www.neurology.org
e-Pub ahead of print on March 12, 2008, at www.neurology.org.
K.H. received support from Forsberg and Aulies Legacy, R.R. holds a postdoctoral fellowship of the Fund for Scientific Research Flanders (FWO-V), and K.N. a PhD fellowship of the Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT-F). Further support for this work included a VA Merit Review Award (C.P.Z.), K08 NS044138 (C.P.Z.), R01 NS37167 (T.F.), Distincio per la promocio de la Reserca Universitaria Generalitad de Catalunya (E.T.), National Medical (NMRC) and Biomedical Research Councils, Singapore (BMRC) (E.K.T.), Internationaal Parkinson Fonds, The Netherlands (V.B.), and National Institute of Neurological Disorders and Stroke P50 NS40256 funded the Udall Clinical (Z.K.W.) and Genetic Cores (M.J.F.), Mayo Clinic Jacksonville.
Disclosure: The authors report no conflicts of interest.
Received August 29, 2007. Accepted in final form October 26, 2007.
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
Letters: Rapid online correspondence
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
Topics Discussed
Alert Me
Recommended articles
Frequency of LRRK2 mutations in early- and late-onset Parkinson disease
The LRRK2 G2019S mutation in Ashkenazi Jews with Parkinson disease
Urinary LRRK2 phosphorylation predicts parkinsonian phenotypes in G2019S LRRK2 carriers
Corticobasal syndrome and primary progressive aphasia as manifestations of LRRK2 gene mutations