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From the Department of Medical and Molecular Genetics (Drs. Foroud and Conneally, and L. Liu, N. Pankratz, and C. Halter), Indiana University Medical Center, Indianapolis; Division of Human Genetics (S.K. Uniacke and Dr. Nichols), Cincinnati Children’s Hospital Medical Center, OH; Department of Neurology (Dr. Rudolph), University of Rochester, NY; Department of Neurosciences, University of California, San Diego, and VA San Diego Healthcare System (Dr. Shults), CA; and Gertrude H. Sergievsky Center and the Department of Neurology (Dr. Marder), College of Physicians and Surgeons, Columbia University, New York, NY.
Address correspondence and reprint requests to Dr. Tatiana Foroud, Indiana University School of Medicine, Department of Medical and Molecular Genetics (IB 130), 975 West Walnut Street, Indianapolis, IN 46202-5251; e-mail: tforoud{at}iupui.edu
Background: The vast majority of the parkin mutations previously identified have been found in individuals with juvenile or early onset PD. Previous screening of later onset PD cohorts has not identified substantial numbers of parkin mutations.
Methods: Families with at least two siblings with PD were ascertained to identify genes contributing to PD susceptibility. Screening of the parkin gene, by both quantitative PCR and exon sequencing, was performed in those families with either early onset PD (age onset 
50 years) or positive lod score with a marker in intron 7 of the parkin gene.
Results: A total of 25 different mutations in the parkin gene were identified in 103 individuals from 47 families. Mutations were found in both parkin alleles in 41 of the individuals, whereas a single mutation in only one of the two parkin alleles was observed in 62 individuals. Thirty-five of the subjects (34%) with a parkin mutation had an age at onset of 60 years or above with 30 of these 35 (86%) having a detectable mutation on only one parkin allele. Few significant clinical differences were observed among the individuals with two, one, or no mutated copies of the parkin gene.
Conclusion: Mutations in the parkin gene occur among individuals with PD with an older age at onset (
60 years) who have a positive family history of the disease. In addition, the clinical findings of parkin-positive individuals are remarkably similar to those without mutations.
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