This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (15)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Neurogenetics  • Movement Disorders  • Parkinson Disease/ Parkinsonian Disorders  • Alert me on articles by topic

Lorraine N. Clark, PhD; Shehla Afridi, MS; Eric Karlins, MS; Yuanjia Wang, PhD; Helen Mejia-Santana, MS; Juliette Harris, PhD; Elan D. Louis, MD, MS; Lucien J. Cote, MD; Howard Andrews, PhD; Stanley Fahn, MD; Cheryl Waters, MD, FRCP; Blair Ford, MD, FRCP; Steven Frucht, MD; Ruth Ottman, PhD; Karen Marder, MD, MPH

Arch Neurol. 2006;63:548-552.

Background  Mutations in parkin are estimated to account for as much as 50% of familial Parkinson disease (PD) and 18% of sporadic PD. Single heterozygous mutations in parkin in both familial and sporadic cases may also increase susceptibility to PD. To our knowledge, all previous studies have been restricted to PD cases; this is the first study to systematically screen the parkin coding regions and exon deletions and duplications in controls.

Objective  To determine the frequency and spectrum of parkin variants in early-onset PD cases (aged 50 years) and controls participating in a familial aggregation study.

Patients and Methods  We sequenced the parkin gene in 101 cases and 105 controls. All cases and controls were also screened for exon deletions and duplications by semiquantitative multiplex polymerase chain reaction.

Results  Thirteen (12.9% [95% confidence interval, 7%-21%]) of the 101 cases had a previously described parkin mutation: 1 was homozygous, 11 were heterozygous, and 1 was a compound heterozygote. The mutations Arg42Pro (exon 2) and Arg275Trp (exon 7) were recurrent. The previously reported synonymous substitution Leu261Leu (c.884A>G) was identified in 4 (3.9%) of 101 cases and 2 (2%) of 105 controls (P = .44). Excluding the synonymous substitution Leu261Leu (heterozygotes), 10 (9.9% [95% confidence interval, 4.6%-17.5%]) carried mutations.

Conclusions  The frequency of mutations among cases that were not selected based on family history of PD is similar to what has previously been reported in sporadic PD. The similar frequency of Leu261Leu in cases and controls suggests it is a normal variant rather than a disease-associated mutation. We confirmed that heterozygous parkin mutations may increase susceptibility for early-onset PD.

Author Affiliations: Taub Institute for Research on Alzheimer's Disease and the Aging Brain (Drs Clark, Louis, and Marder and Ms Afridi), Departments of Pathology (Dr Clark), Statistics (Dr Wang), Neurology (Drs Harris, Louis, Cote, Fahn, Waters, Ford, Frucht, and Marder), and Psychiatry (Dr Marder) and Gertrude H. Sergievsky Center (Mr Karlins, Ms Mejia-Santana, and Drs Louis, Cote, Andrews, Ottman, and Marder), College of Physicians and Surgeons, Epidemiology Department, Mailman School of Public Health (Drs Andrews and Ottman), and The Epidemiology of Brain Disorders Department, New York State Psychiatric Institute (Dr Ottman), Columbia University, New York, NY.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

How to Predict the Risk of Parkinson Disease in Relatives of Parkin Mutation Carriers: A Complex Puzzle of Age, Penetrance, and Number of Mutated Alleles
Klein and Ziegler
Arch Neurol 2008;65:443-444.
FULL TEXT  

Risk of Parkinson Disease in Carriers of Parkin Mutations: Estimation Using the Kin-Cohort Method
Wang et al.
Arch Neurol 2008;65:467-474.
ABSTRACT | FULL TEXT  

Rare heterozygous parkin variants in French early-onset Parkinson disease patients and controls
Lesage et al.
J. Med. Genet. 2008;45:43-46.
ABSTRACT | FULL TEXT  

Parkinson disease, 10 years after its genetic revolution: Multiple clues to a complex disorder
Klein and Schlossmacher
Neurology 2007;69:2093-2104.
ABSTRACT | FULL TEXT  

Mutations in the glucocerebrosidase gene are associated with early-onset Parkinson disease
Clark et al.
Neurology 2007;69:1270-1277.
ABSTRACT | FULL TEXT  

Drosophila Overexpressing Parkin R275W Mutant Exhibits Dopaminergic Neuron Degeneration and Mitochondrial Abnormalities
Wang et al.
J. Neurosci. 2007;27:8563-8570.
ABSTRACT | FULL TEXT  

Nonparametric estimation of age-at-onset distributions from censored kin-cohort data
Wang et al.
Biometrika 2007;94:403-403.
ABSTRACT | FULL TEXT  

Frequency of LRRK2 mutations in early- and late-onset Parkinson disease
Clark et al.
Neurology 2006;67:1786-1791.
ABSTRACT | FULL TEXT