Heterozygous parkin point mutations are as common in control subjects as in Parkinson's patients
Article first published online: 22 DEC 2006
Copyright © 2006 American Neurological Association
Annals of Neurology
Volume 61, Issue 1, pages 47–54, January 2007
How to Cite
Kay, D. M., Moran, D., Moses, L., Poorkaj, P., Zabetian, C. P., Nutt, J., Factor, S. A., Yu, C.-E., Montimurro, J. S., Keefe, R. G., Schellenberg, G. D. and Payami, H. (2007), Heterozygous parkin point mutations are as common in control subjects as in Parkinson's patients. Ann Neurol., 61: 47–54. doi: 10.1002/ana.21039
- Issue published online: 29 JAN 2007
- Article first published online: 22 DEC 2006
- Manuscript Accepted: 13 OCT 2006
- Manuscript Revised: 29 AUG 2006
- Manuscript Received: 3 APR 2006
- NIH (National Institute of Neurological Disorders and Stroke). Grant Number: NS R01-36960
- National Institute of Aging, Jeffrey Kaye. Grant Number: AG 08017
- Michael J. Fox Foundation Edmond J. Safra Global Genetics Consortia Grant
- Veterans' Administration PADRECC Grant
- VA Research Funds
- Geriatric Research Education and Clinical Center at the VA Puget Sound Health Care System
- Genomics Institute Core Facilities at the New York State Department of Health Wadsworth Center
Homozygous or compound heterozygous parkin mutations cause juvenile parkinsonism. Heterozygous parkin mutations are also found in patients with typical Parkinson's disease (PD), but it is unclear whether a single “mutation” in a patient is related to disease or is coincidental, because the mutation frequency in control subjects is unknown. We present a comprehensive sequence analysis of parkin in control subjects.
A total of 302 patients and 301 control subjects were sequenced, and findings were replicated in 1,260 additional patients and 1,657 control subjects.
Thirty-four variants were detected, of which 21 were novel; 12 were polymorphisms and 22 were rare variants. Patients and control subjects did not differ in the frequency, type, or functional location of the variants. Even P437L, a common mutation thought to be pathogenic, was present in unaffected control subjects.
parkin point mutations are not exclusive to PD. The mere presence of a single point mutation in a patient, in the absence of a second mutation, should not be taken as a cause of disease unless corroborated by family data and functional studies. This study does not support the notion that heterozygous parkin sequence variants (mutations or polymorphisms) are risk factors for PD. Whether heterozygous dosage anomalies are associated with PD remains to be determined. Ann Neurol 2006