| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
From the Departments of Human Genetics (Drs. Hedrich, Schwinger, and Klein, and A. Djarmati, N. Schäfer, and C. Wellenbrock) and Neurology (Drs. Hedrich, Vieregge, and Klein, and A. Djarmati, N. Schäfer, and C. Wellenbrock), University of Lübeck, Germany; Faculty of Biology (A. Djarmati), University of Belgrade, Serbia; Department of Medical Genetics (Drs. Hering and Riess), University Tübingen, Germany; Department of Neurology (Drs. Weiss and Noth), University of Aachen, Germany; Department of Neurology (Dr. Hilker), University of Cologne, Germany; Department of Molecular Genetics (Dr. Ozelius), Albert Einstein College of Medicine, Bronx, NY; Genetic-Epidemiologic Unit (Drs. Heutink and Bonifati), Department of Clinical Genetics, Department of Epidemiology & Biostatistics, Eramus Medical Center Rotterdam, the Netherlands; Department of Neurological Sciences (Dr. Bonifati), "La Sapienza" University, Rome, Italy; Division of Neurology (Dr. Lang), Department of Medicine, University of Toronto, and Toronto Western Hospital, Canada; Department of Neurology (Dr. Bressman), Beth Israel Medical Center, New York, NY; and Department of Neurology (Dr. Pramstaller), Regional General Hospital, Bolzano, Italy.
Address correspondence and reprint requests to Dr. Christine Klein, Department of Neurology, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany; e-mail: klein_ch{at}neuro.mu-luebeck.de
Background: Mutations in the Parkin gene (PARK2) are the most commonly identified cause of recessively inherited early-onset Parkinson disease (EOPD) but account for only a portion of cases. DJ-1 (PARK7) was recently reported as a second gene associated with recessively inherited PD with a homozygous exon deletion and a homozygous point mutation in two families.
Methods: To investigate the frequency of DJ-1 mutations, the authors performed mutational analysis of all six coding exons of DJ-1 in 100 EOPD patients. For the detection of exon rearrangements, the authors developed a quantitative duplex PCR assay. Denaturing high performance liquid chromatography analysis was used to screen for point mutations and small deletions. Further, Parkin analysis was performed as previously described.
Results: The authors identified two carriers of single heterozygous loss-of-function DJ-1 mutations, including a heterozygous deletion of exons 5 to 7 and an 11-base pair deletion, removing the invariant donor splice site in intron 5. Interestingly, both DJ-1 mutations identified in this study were found in the heterozygous state only. The authors also detected a polymorphism (R98Q) in 1.5% of the chromosomes in both the patient and control group. In the same patient sample, 17 cases were detected with mutations in the Parkin gene.
Conclusions: Mutations in DJ-1 are less frequent than mutations in Parkin in EOPD patients but should be considered as a possible cause of EOPD. The effect of single heterozygous mutations in DJ-1 on the nigrostriatal system, as described for heterozygous changes in Parkin and PARK6, remains to be elucidated.
Received July 25, 2003. Accepted in final form December 4, 2003.
*The first two authors contributed equally to this study.
This article has been cited by other articles:
|
|
 |
|
  S. Ishikawa, T. Taira, T. Niki, K. Takahashi-Niki, C. Maita, H. Maita, H. Ariga, and S. M. M. Iguchi-Ariga Oxidative Status of DJ-1-dependent Activation of Dopamine Synthesis through Interaction of Tyrosine Hydroxylase and 4-Dihydroxy-L-phenylalanine (L-DOPA) Decarboxylase with DJ-1 J. Biol. Chem., October 16, 2009; 284(42): 28832 - 28844. [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]
|
|
|
|
 |
|
 E. Moro, J. Volkmann, I. R. Konig, S. Winkler, A. Hiller, S. Hassin-Baer, J. Herzog, A. Schnitzler, K. Lohmann, M. O. Pinsker, et al. Bilateral subthalamic stimulation in Parkin and PINK1 parkinsonism Neurology, April 1, 2008; 70(14): 1186 - 1191. [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]
|
|
|
|
|
|
C. Klein and M. G. Schlossmacher Parkinson disease, 10 years after its genetic revolution: Multiple clues to a complex disorder Neurology, November 27, 2007; 69(22): 2093 - 2104. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Thomas and M. F. Beal Parkinson's disease Hum. Mol. Genet., October 15, 2007; 16(R2): R183 - R194. [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]
|
|
|
|
 |
|
 E. Andres-Mateos, C. Perier, L. Zhang, B. Blanchard-Fillion, T. M. Greco, B. Thomas, H. S. Ko, M. Sasaki, H. Ischiropoulos, S. Przedborski, et al. DJ-1 gene deletion reveals that DJ-1 is an atypical peroxiredoxin-like peroxidase PNAS, September 11, 2007; 104(37): 14807 - 14812. [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]
|
|
|
|
|
|
N. Zhong, C. Y. Kim, P. Rizzu, C. Geula, D. R. Porter, E. N. Pothos, F. Squitieri, P. Heutink, and J. Xu DJ-1 Transcriptionally Up-regulates the Human Tyrosine Hydroxylase by Inhibiting the Sumoylation of Pyrimidine Tract-binding Protein-associated Splicing Factor J. Biol. Chem., July 28, 2006; 281(30): 20940 - 20948. [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]
|
|
|
|
|
|
L. Chen, B. Cagniard, T. Mathews, S. Jones, H. C. Koh, Y. Ding, P. M. Carvey, Z. Ling, U. J. Kang, and X. Zhuang Age-dependent Motor Deficits and Dopaminergic Dysfunction in DJ-1 Null Mice J. Biol. Chem., June 3, 2005; 280(22): 21418 - 21426. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Xu, N. Zhong, H. Wang, J. E. Elias, C. Y. Kim, I. Woldman, C. Pifl, S. P. Gygi, C. Geula, and B. A. Yankner The Parkinson's disease-associated DJ-1 protein is a transcriptional co-activator that protects against neuronal apoptosis Hum. Mol. Genet., May 1, 2005; 14(9): 1231 - 1241. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Moore, L. Zhang, J. Troncoso, M. K. Lee, N. Hattori, Y. Mizuno, T. M. Dawson, and V. L. Dawson Association of DJ-1 and parkin mediated by pathogenic DJ-1 mutations and oxidative stress Hum. Mol. Genet., January 1, 2005; 14(1): 71 - 84. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Hatano, K. Sato, B. Elibol, H. Yoshino, Y. Yamamura, V. Bonifati, H. Shinotoh, M. Asahina, S. Kobayashi, A. R. Ng, et al. PARK6-linked autosomal recessive early-onset parkinsonism in Asian populations Neurology, October 26, 2004; 63(8): 1482 - 1485. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Maraganore, K. Wilkes, T. G. Lesnick, K. J. Strain, M. de Andrade, W. A. Rocca, J. H. Bower, J. E. Ahlskog, S. Lincoln, and M. J. Farrer A limited role for DJ1 in Parkinson disease susceptibility Neurology, August 10, 2004; 63(3): 550 - 553. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Bandmann DJ-1: The second gene for early onset Parkinson disease Neurology, February 10, 2004; 62(3): 357 - 358. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
