| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
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.
This article has been cited by other articles:
|
|
 |
|
  N. Pankratz, D. K. Kissell, M. W. Pauciulo, C. A. Halter, A. Rudolph, R. F. Pfeiffer, K. S. Marder, T. Foroud, W. C. Nichols, and For the Parkinson Study Group-PROGENI Investigator Parkin dosage mutations have greater pathogenicity in familial PD than simple sequence mutations Neurology, July 28, 2009; 73(4): 279 - 286. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. C. Nichols, D. K. Kissell, N. Pankratz, M. W. Pauciulo, V. E. Elsaesser, K. A. Clark, C. A. Halter, A. Rudolph, J. Wojcieszek, R. F. Pfeiffer, et al. Variation in GIGYF2 is not associated with Parkinson disease Neurology, June 2, 2009; 72(22): 1886 - 1892. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J Brooks, J Ding, J Simon-Sanchez, C Paisan-Ruiz, A B Singleton, and S W Scholz Parkin and PINK1 mutations in early-onset Parkinson's disease: comprehensive screening in publicly available cases and control J. Med. Genet., June 1, 2009; 46(6): 375 - 381. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. A. Hristova, S. A. Beasley, R. J. Rylett, and G. S. Shaw Identification of a Novel Zn2+-binding Domain in the Autosomal Recessive Juvenile Parkinson-related E3 Ligase Parkin J. Biol. Chem., May 29, 2009; 284(22): 14978 - 14986. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X.-H. Lu, S. M. Fleming, B. Meurers, L. C. Ackerson, F. Mortazavi, V. Lo, D. Hernandez, D. Sulzer, G. R. Jackson, N. T. Maidment, et al. Bacterial Artificial Chromosome Transgenic Mice Expressing a Truncated Mutant Parkin Exhibit Age-Dependent Hypokinetic Motor Deficits, Dopaminergic Neuron Degeneration, and Accumulation of Proteinase K-Resistant {alpha}-Synuclein J. Neurosci., February 18, 2009; 29(7): 1962 - 1976. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Pan, S. Kondo, W. Le, and J. Jankovic The role of autophagy-lysosome pathway in neurodegeneration associated with Parkinson's disease Brain, August 1, 2008; 131(8): 1969 - 1978. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Schroeder, M. Walter, D. Berg, P. Leitner, P. Bauer, Z. Kohl, J. Winkler, O. Riess, and M. Bonin High-Throughput Homogeneous Mass Cleave Assay Technology for the Diagnosis of Autosomal Recessive Parkinson's Disease J. Mol. Diagn., May 1, 2008; 10(3): 217 - 224. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Wang, L. N. Clark, E. D. Louis, H. Mejia-Santana, J. Harris, L. J. Cote, C. Waters, H. Andrews, B. Ford, S. Frucht, et al. Risk of Parkinson Disease in Carriers of Parkin Mutations: Estimation Using the Kin-Cohort Method Arch Neurol, April 1, 2008; 65(4): 467 - 474. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S Lesage, E Lohmann, F Tison, F Durif, A Durr, A Brice, and for the French Parkinson's Disease Genetics Study Rare heterozygous parkin variants in French early-onset Parkinson disease patients and controls J. Med. Genet., January 1, 2008; 45(1): 43 - 46. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. N. Clark, B. M. Ross, Y. Wang, H. Mejia-Santana, J. Harris, E. D. Louis, L. J. Cote, H. Andrews, S. Fahn, C. Waters, et al. Mutations in the glucocerebrosidase gene are associated with early-onset Parkinson disease Neurology, September 18, 2007; 69(12): 1270 - 1277. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-K. Sang, H.-Y. Chang, G. M. Lawless, A. Ratnaparkhi, L. Mee, L. C. Ackerson, N. T. Maidment, D. E. Krantz, and G. R. Jackson A Drosophila Model of Mutant Human Parkin-Induced Toxicity Demonstrates Selective Loss of Dopaminergic Neurons and Dependence on Cellular Dopamine J. Neurosci., January 31, 2007; 27(5): 981 - 992. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Hampe, H. Ardila-Osorio, M. Fournier, A. Brice, and O. Corti Biochemical analysis of Parkinson's disease-causing variants of Parkin, an E3 ubiquitin-protein ligase with monoubiquitylation capacity Hum. Mol. Genet., July 1, 2006; 15(13): 2059 - 2075. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sun, J. C. Latourelle, G. F. Wooten, M. F. Lew, C. Klein, H. A. Shill, L. I. Golbe, M. H. Mark, B. A. Racette, J. S. Perlmutter, et al. Influence of heterozygosity for parkin mutation on onset age in familial Parkinson disease: the GenePD study. Arch Neurol, June 1, 2006; 63(6): 826 - 832. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. N. Clark, S. Afridi, E. Karlins, Y. Wang, H. Mejia-Santana, J. Harris, E. D. Louis, L. J. Cote, H. Andrews, S. Fahn, et al. Case-control study of the parkin gene in early-onset Parkinson disease. Arch Neurol, April 1, 2006; 63(4): 548 - 552. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Deng, W.-D. Le, C. B. Hunter, W. G. Ondo, Y. Guo, W.-J. Xie, and J. Jankovic Heterogeneous Phenotype in a Family With Compound Heterozygous Parkin Gene Mutations Arch Neurol, February 1, 2006; 63(2): 273 - 277. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Wang, H. S. Ko, B. Thomas, F. Tsang, K. C.M. Chew, S.-P. Tay, M. W.L. Ho, T.-M. Lim, T.-W. Soong, O. Pletnikova, et al. Stress-induced alterations in parkin solubility promote parkin aggregation and compromise parkin's protective function Hum. Mol. Genet., December 15, 2005; 14(24): 3885 - 3897. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R H Madegowda, A Kishore, and A Anand Mutational screening of the parkin gene among South Indians with early onset Parkinson's disease J. Neurol. Neurosurg. Psychiatry, November 1, 2005; 76(11): 1588 - 1590. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Foroud LRRK2: Both a cause and a risk factor for Parkinson disease? Neurology, September 13, 2005; 65(5): 664 - 665. [Full Text] [PDF]
|
|
|
|
|
|
S. R. Sriram, X. Li, H. S. Ko, K. K.K. Chung, E. Wong, K. L. Lim, V. L. Dawson, and T. M. Dawson Familial-associated mutations differentially disrupt the solubility, localization, binding and ubiquitination properties of parkin Hum. Mol. Genet., September 1, 2005; 14(17): 2571 - 2586. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Desautels, G. Turecki, J. Montplaisir, L. Xiong, A. S. Walters, B. L. Ehrenberg, K. Brisebois, A. K. Desautels, Y. Gingras, W. G. Johnson, et al. Restless Legs Syndrome: Confirmation of Linkage to Chromosome 12q, Genetic Heterogeneity, and Evidence of Complexity Arch Neurol, April 1, 2005; 62(4): 591 - 596. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Marin, J. I. Lucas, A.-C. Gradilla, and A. Ferrus Parkin and relatives: the RBR family of ubiquitin ligases Physiol Genomics, May 19, 2004; 17(3): 253 - 263. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Pankratz, S. K. Uniacke, C. A. Halter, A. Rudolph, C. W. Shults, P. M. Conneally, T. Foroud, W. C. Nichols, and the Parkinson Study Group Genes influencing Parkinson disease onset: Replication of PARK3 and identification of novel loci Neurology, May 11, 2004; 62(9): 1616 - 1618. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Palacino, D. Sagi, M. S. Goldberg, S. Krauss, C. Motz, M. Wacker, J. Klose, and J. Shen Mitochondrial Dysfunction and Oxidative Damage in parkin-deficient Mice J. Biol. Chem., April 30, 2004; 279(18): 18614 - 18622. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. F. Mata, P. J. Lockhart, and M. J. Farrer Parkin genetics: one model for Parkinson's disease Hum. Mol. Genet., April 1, 2004; 13(90001): R127 - 133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D G Healy, P M Abou-Sleiman, E M Valente, W P Gilks, K Bhatia, N Quinn, A J Lees, and N W Wood DJ-1 mutations in Parkinson's disease J. Neurol. Neurosurg. Psychiatry, January 1, 2004; 75(1): 144 - 145. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Pankratz, W. C. Nichols, S. K. Uniacke, C. Halter, J. Murrell, A. Rudolph, C. W. Shults, P. M. Conneally, T. Foroud, and the Parkinson Study Group Genome-wide linkage analysis and evidence of gene-by-gene interactions in a sample of 362 multiplex Parkinson disease families Hum. Mol. Genet., October 16, 2003; 12(20): 2599 - 2608. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Parkin Mutations in Late-Onset PD with Family History Journal Watch Neurology, August 21, 2003; 2003(821): 3 - 3. [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
