FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 342:1560-1567 May 25, 2000 Number 21 Next

	Full Text PDF Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Mutations in the parkin gene have recently been identified in patients with early-onset Parkinson's disease, but the frequency of the mutations and the associated phenotype have not been assessed in a large series of patients.

Methods We studied 73 families in which at least one of the affected family members was affected at or before the age of 45 years and had parents who were not affected, as well as 100 patients with isolated Parkinson's disease that began at or before the age of 45 years. All subjects were screened for mutations in the parkin gene with use of a semiquantitative polymerase-chain-reaction assay that simultaneously amplified several exons. We sequenced the coding exons in a subgroup of patients. We also compared the clinical features of patients with parkin mutations and those without mutations.

Results Among the families with early-onset Parkinson's disease, 36 (49 percent) had parkin mutations. The age at onset ranged from 7 to 58 years. Among the patients with isolated Parkinson's disease, mutations were detected in 10 of 13 patients (77 percent) with an age at onset of 20 years or younger, but in only 2 of 64 patients (3 percent) with an age at onset of more than 30 years. The mean (±SD) age at onset in the patients with parkin mutations was younger than that in those without mutations (32±11 vs. 42± 11 years, P<0.001), and they were more likely to have symmetric involvement and dystonia at onset, to have hyperreflexia at onset or later, to have a good response to levodopa therapy, and to have levodopa-induced dyskinesias during treatment. Nineteen different rearrangements of exons (deletions and multiplications) and 16 different point mutations were detected.

Conclusions Mutations in the parkin gene are a major cause of early-onset autosomal recessive familial Parkinson's disease and isolated juvenile-onset Parkinson's disease (at or before the age of 20 years). Accurate diagnosis of these cases cannot be based only on the clinical manifestations of the disease.

Source Information

From INSERM Unité 289, Hôpital de la Salpêtrière, Paris (C.B.L., A.D., Y.A., A.B.); the Dipartimento di Scienze Neurologiche, Università La Sapienza, Rome (V.B., G.M.); the Institute of Neurology, London (J.V., N.W.W.); the Dipartimento di Scienze Neurologiche, Università Federico II, Naples, Italy (G.D.); the Neurologische Klinik, Klinikum Großhadern, Ludwig Maximilians Universität, Munich, Germany (T.G.); the Department of Epidemiology and Biostatistics, Erasmus University Medical School, Rotterdam, the Netherlands (B.S.H); and Evry Genomics Center, Aventis Pharma France, Evry, France (P.D.). Other authors were D. Nicholl, M.D. (University of Birmingham, Birmingham, United Kingdom); M.M.B. Breteler, M.D. (Erasmus University Medical School, Rotterdam, the Netherlands); B.A. Oostra, M.D. (Erasmus University, Rotterdam, the Netherlands); M. De Mari, M.D. (Università degli Studi di Bari, Bari, Italy); R. Marconi, M.D. (Ospedale della Misericordia, Grosseto, Italy); A. Filla, M.D. (Università Federico II, Naples, Italy); A.-M. Bonnet, M.D. (Hôpital de la Salpêtrière, Paris); E. Broussolle, M.D. (Hôpital Pierre Wertheimer, Lyons, France); P. Pollak, M.D. (Centre Hospitalier Universitaire de Grenoble, Grenoble, France); O. Rascol, M.D. (INSERM Unité 455, Toulouse, France); and M. Rosier, Ph.D., and I. Arnould, Ph.D. (Aventis Pharma France, Evry, France).

Address reprint requests to Dr. Brice at INSERM Unité 289, Hôpital de la Salpêtrière, 47 Blvd. de l'Hôpital, 75651 Paris CEDEX 13, France, or at brice{at}ccr.jussieu.fr.

Full Text of this Article

This article has been cited by other articles:

• Kumazawa, R., Tomiyama, H., Li, Y., Imamichi, Y., Funayama, M., Yoshino, H., Yokochi, F., Fukusako, T., Takehisa, Y., Kashihara, K., Kondo, T., Elibol, B., Bostantjopoulou, S., Toda, T., Takahashi, H., Yoshii, F., Mizuno, Y., Hattori, N. (2008). Mutation Analysis of the PINK1 Gene in 391 Patients With Parkinson Disease. Arch Neurol 65: 802-808 [Abstract] [Full Text]  
• Schroeder, C., Walter, M., Berg, D., Leitner, P., Bauer, P., Kohl, Z., Winkler, J., Riess, O., Bonin, M. (2008). High-Throughput Homogeneous Mass Cleave Assay Technology for the Diagnosis of Autosomal Recessive Parkinson's Disease. J. Mol. Diagn. 10: 217-224 [Abstract] [Full Text]  
• Klein, C., Ziegler, A. (2008). 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. Arch Neurol 65: 443-444 [Full Text]  
• Wang, Y., Clark, L. N., Louis, E. D., Mejia-Santana, H., Harris, J., Cote, L. J., Waters, C., Andrews, H., Ford, B., Frucht, S., Fahn, S., Ottman, R., Rabinowitz, D., Marder, K. (2008). Risk of Parkinson Disease in Carriers of Parkin Mutations: Estimation Using the Kin-Cohort Method. Arch Neurol 65: 467-474 [Abstract] [Full Text]  
• Moro, E., Volkmann, J., Konig, I. R., Winkler, S., Hiller, A., Hassin-Baer, S., Herzog, J., Schnitzler, A., Lohmann, K., Pinsker, M. O., Voges, J., Djarmatic, A., Seibler, P., Lozano, A. M., Rogaeva, E., Lang, A. E., Deuschl, G., Klein, C. (2008). Bilateral subthalamic stimulation in Parkin and PINK1 parkinsonism. Neurology 70: 1186-1191 [Abstract] [Full Text]  
• Lee, J. T., Wheeler, T. C., Li, L., Chin, L.-S. (2008). Ubiquitination of {alpha}-synuclein by Siah-1 promotes {alpha}-synuclein aggregation and apoptotic cell death. Hum Mol Genet 17: 906-917 [Abstract] [Full Text]  
• Solano, R. M., Casarejos, M. J., Menendez-Cuervo, J., Rodriguez-Navarro, J. A., Garcia de Yebenes, J., Mena, M. A. (2008). Glial Dysfunction in Parkin Null Mice: Effects of Aging. J. Neurosci. 28: 598-611 [Abstract] [Full Text]  
• Lesage, S, Lohmann, E, Tison, F, Durif, F, Durr, A, Brice, A, for the French Parkinson's Disease Genetics Study, (2008). Rare heterozygous parkin variants in French early-onset Parkinson disease patients and controls. J. Med. Genet. 45: 43-46 [Abstract] [Full Text]  
• Klein, C., Schlossmacher, M. G. (2007). Parkinson disease, 10 years after its genetic revolution: Multiple clues to a complex disorder. Neurology 69: 2093-2104 [Abstract] [Full Text]  
• Cookson, M. R., Dauer, W., Dawson, T., Fon, E. A., Guo, M., Shen, J. (2007). The Roles of Kinases in Familial Parkinson's Disease. J. Neurosci. 27: 11865-11868 [Abstract] [Full Text]  
• Inzelberg, R., Jankovic, J. (2007). Are Parkinson disease patients protected from some but not all cancers?. Neurology 69: 1542-1550 [Abstract] [Full Text]  
• Olzmann, J. A., Li, L., Chudaev, M. V., Chen, J., Perez, F. A., Palmiter, R. D., Chin, L.-S. (2007). Parkin-mediated K63-linked polyubiquitination targets misfolded DJ-1 to aggresomes via binding to HDAC6. J. Cell Biol. 178: 1025-1038 [Abstract] [Full Text]  
• Inoue, H., Lin, L., Lee, X., Shao, Z., Mendes, S., Snodgrass-Belt, P., Sweigard, H., Engber, T., Pepinsky, B., Yang, L., Beal, M. F., Mi, S., Isacson, O. (2007). Inhibition of the leucine-rich repeat protein LINGO-1 enhances survival, structure, and function of dopaminergic neurons in Parkinson's disease models. Proc. Natl. Acad. Sci. USA 104: 14430-14435 [Abstract] [Full Text]  
• Binkofski, F., Reetz, K., Gaser, C., Hilker, R., Hagenah, J., Hedrich, K., van Eimeren, T., Thiel, A., Buchel, C., Pramstaller, P. P., Siebner, H. R., Klein, C. (2007). Morphometric fingerprint of asymptomatic Parkin and PINK1 mutation carriers in the basal ganglia. Neurology 69: 842-850 [Abstract] [Full Text]  
• Wang, C., Lu, R., Ouyang, X., Ho, M. W. L., Chia, W., Yu, F., Lim, K.-L. (2007). Drosophila Overexpressing Parkin R275W Mutant Exhibits Dopaminergic Neuron Degeneration and Mitochondrial Abnormalities. J. Neurosci. 27: 8563-8570 [Abstract] [Full Text]  
• Joch, M., Ase, A. R., Chen, C. X.-Q., MacDonald, P. A., Kontogiannea, M., Corera, A. T., Brice, A., Seguela, P., Fon, E. A. (2007). Parkin-mediated Monoubiquitination of the PDZ Protein PICK1 Regulates the Activity of Acid-sensing Ion Channels. Mol. Biol. Cell 18: 3105-3118 [Abstract] [Full Text]  
• Wang, Y., Clark, L. N., Marder, K., Rabinowitz, D. (2007). Nonparametric estimation of age-at-onset distributions from censored kin-cohort data. Biometrika 94: 403-403 [Abstract] [Full Text]  
• Deng, H., Le, W., Jankovic, J. (2007). Genetics of essential tremor. Brain 130: 1456-1464 [Abstract] [Full Text]  
• Mandemakers, W., Morais, V. A., De Strooper, B. (2007). A cell biological perspective on mitochondrial dysfunction in Parkinson disease and other neurodegenerative diseases. J. Cell Sci. 120: 1707-1716 [Abstract] [Full Text]  
• Wong, E. S. P., Tan, J. M. M., Wang, C., Zhang, Z., Tay, S.-P., Zaiden, N., Ko, H. S., Dawson, V. L., Dawson, T. M., Lim, K.-L. (2007). Relative Sensitivity of Parkin and Other Cysteine-containing Enzymes to Stress-induced Solubility Alterations. J. Biol. Chem. 282: 12310-12318 [Abstract] [Full Text]  
• Deng, H., Le, W.-D., Hunter, C. B., Mejia, N., Xie, W.-J., Jankovic, J. (2007). A Family With Parkinson Disease, Essential Tremor, Bell Palsy, and Parkin Mutations. Arch Neurol 64: 421-424 [Abstract] [Full Text]  
• Beasley, S. A., Hristova, V. A., Shaw, G. S. (2007). From the Cover: Structure of the Parkin in-between-ring domain provides insights for E3-ligase dysfunction in autosomal recessive Parkinson's disease. Proc. Natl. Acad. Sci. USA 104: 3095-3100 [Abstract] [Full Text]  
• Toft, M, Myhre, R, Pielsticker, L, White, L R, Aasly, J O, Farrer, M J (2007). PINK1 mutation heterozygosity and the risk of Parkinson's disease. J. Neurol. Neurosurg. Psychiatry 78: 82-84 [Abstract] [Full Text]  
• Chinnery, P. F., Crompton, D. E., Birchall, D., Jackson, M. J., Coulthard, A., Lombes, A., Quinn, N., Wills, A., Fletcher, N., Mottershead, J. P., Cooper, P., Kellett, M., Bates, D., Burn, J. (2007). Clinical features and natural history of neuroferritinopathy caused by the FTL1 460InsA mutation. Brain 130: 110-119 [Abstract] [Full Text]  
• Reinstein, E., Ciechanover, A. (2006). Narrative review: protein degradation and human diseases: the ubiquitin connection.. ANN INTERN MED 145: 676-684 [Abstract] [Full Text]  
• Tan, E.-K., Jankovic, J. (2006). Genetic testing in Parkinson disease: promises and pitfalls.. Arch Neurol 63: 1232-1237 [Full Text]  
• Chung, E. J., Ki, C.-S., Lee, W. Y., Kim, I.-S., Kim, J.-Y. (2006). Clinical Features and Gene Analysis in Korean Patients With Early-Onset Parkinson Disease.. Arch Neurol 63: 1170-1174 [Abstract] [Full Text]  
• Hampe, C., Ardila-Osorio, H., Fournier, M., Brice, A., Corti, O. (2006). Biochemical analysis of Parkinson's disease-causing variants of Parkin, an E3 ubiquitin-protein ligase with monoubiquitylation capacity. Hum Mol Genet 15: 2059-2075 [Abstract] [Full Text]  
• Beffert, U., Rosenberg, R. N. (2006). Increased risk for heterozygotes in recessive Parkinson disease.. Arch Neurol 63: 807-808 [Full Text]  
• Sun, M., Latourelle, J. C., Wooten, G. F., Lew, M. F., Klein, C., Shill, H. A., Golbe, L. I., Mark, M. H., Racette, B. A., Perlmutter, J. S., Parsian, A., Guttman, M., Nicholson, G., Xu, G., Wilk, J. B., Saint-Hilaire, M. H., DeStefano, A. L., Prakash, R., Williamson, S., Suchowersky, O., Labelle, N., Growdon, J. H., Singer, C., Watts, R. L., Goldwurm, S., Pezzoli, G., Baker, K. B., Pramstaller, P. P., Burn, D. J., Chinnery, P. F., Sherman, S., Vieregge, P., Litvan, I., Gillis, T., MacDonald, M. E., Myers, R. H., Gusella, J. F. (2006). Influence of heterozygosity for parkin mutation on onset age in familial Parkinson disease: the GenePD study.. Arch Neurol 63: 826-832 [Abstract] [Full Text]  
• Poewe, W. (2006). The need for neuroprotective therapies in Parkinson's disease: A clinical perspective. Neurology 66: S2-S9 [Abstract] [Full Text]  
• Jenner, P., Olanow, C. W. (2006). The pathogenesis of cell death in Parkinson's disease. Neurology 66: S24-S36 [Abstract] [Full Text]  
• von Coelln, R., Thomas, B., Andrabi, S. A., Lim, K. L., Savitt, J. M., Saffary, R., Stirling, W., Bruno, K., Hess, E. J., Lee, M. K., Dawson, V. L., Dawson, T. M. (2006). Inclusion body formation and neurodegeneration are parkin independent in a mouse model of alpha-synucleinopathy.. J. Neurosci. 26: 3685-3696 [Abstract] [Full Text]  
• Clark, L. N., Afridi, S., Karlins, E., Wang, Y., Mejia-Santana, H., Harris, J., Louis, E. D., Cote, L. J., Andrews, H., Fahn, S., Waters, C., Ford, B., Frucht, S., Ottman, R., Marder, K. (2006). Case-control study of the parkin gene in early-onset Parkinson disease.. Arch Neurol 63: 548-552 [Abstract] [Full Text]  
• Klein, C. (2006). Implications of genetics on the diagnosis and care of patients with Parkinson disease.. Arch Neurol 63: 328-334 [Abstract] [Full Text]  
• Ibanez, P., Lesage, S., Lohmann, E., Thobois, S., Michele, G. D., Borg, M., Agid, Y., Durr, A., Brice, A., and the French Parkinson's Disease Genetics Study, (2006). Mutational analysis of the PINK1 gene in early-onset parkinsonism in Europe and North Africa. Brain 129: 686-694 [Abstract] [Full Text]  
• Deng, H., Le, W.-D., Hunter, C. B., Ondo, W. G., Guo, Y., Xie, W.-J., Jankovic, J. (2006). Heterogeneous Phenotype in a Family With Compound Heterozygous Parkin Gene Mutations. Arch Neurol 63: 273-277 [Abstract] [Full Text]  
• Lesage, S., Durr, A., Tazir, M., Lohmann, E., Leutenegger, A.-L., Janin, S., Pollak, P., Brice, A., the French Parkinson's Disease Genetics Study Grou, (2006). LRRK2 G2019S as a Cause of Parkinson's Disease in North African Arabs. NEJM 354: 422-423 [Full Text]  
• Skipper, L., Li, Y., Bonnard, C., Pavanni, R., Yih, Y., Chua, E., Sung, W.-K., Tan, L., Wong, M.-C., Tan, E.-K., Liu, J. (2005). Comprehensive evaluation of common genetic variation within LRRK2 reveals evidence for association with sporadic Parkinson's disease. Hum Mol Genet 14: 3549-3556 [Abstract] [Full Text]  
• Madegowda, R H, Kishore, A, Anand, A (2005). Mutational screening of the parkin gene among South Indians with early onset Parkinson's disease. J. Neurol. Neurosurg. Psychiatry 76: 1588-1590 [Abstract] [Full Text]  
• Sriram, S. R., Li, X., Ko, H. S., Chung, K. K.K., Wong, E., Lim, K. L., Dawson, V. L., Dawson, T. M. (2005). Familial-associated mutations differentially disrupt the solubility, localization, binding and ubiquitination properties of parkin. Hum Mol Genet 14: 2571-2586 [Abstract] [Full Text]  
• Ko, H. S., von Coelln, R., Sriram, S. R., Kim, S. W., Chung, K. K. K., Pletnikova, O., Troncoso, J., Johnson, B., Saffary, R., Goh, E. L., Song, H., Park, B.-J., Kim, M. J., Kim, S., Dawson, V. L., Dawson, T. M. (2005). Accumulation of the Authentic Parkin Substrate Aminoacyl-tRNA Synthetase Cofactor, p38/JTV-1, Leads to Catecholaminergic Cell Death. J. Neurosci. 25: 7968-7978 [Abstract] [Full Text]  
• Hague, S M, Klaffke, S, Bandmann, O (2005). Neurodegenerative disorders: Parkinson's disease and Huntington's disease. J. Neurol. Neurosurg. Psychiatry 76: 1058-1063 [Abstract] [Full Text]  
• Li, Y., Tomiyama, H., Sato, K., Hatano, Y., Yoshino, H., Atsumi, M., Kitaguchi, M., Sasaki, S., Kawaguchi, S., Miyajima, H., Toda, T., Mizuno, Y., Hattori, N. (2005). Clinicogenetic study of PINK1 mutations in autosomal recessive early-onset parkinsonism. Neurology 64: 1955-1957 [Abstract] [Full Text]  
• Greene, J. C., Whitworth, A. J., Andrews, L. A., Parker, T. J., Pallanck, L. J. (2005). Genetic and genomic studies of Drosophila parkin mutants implicate oxidative stress and innate immune responses in pathogenesis. Hum Mol Genet 14: 799-811 [Abstract] [Full Text]  
• (2005). Park2tm1Rpa Mice. Sci Aging Knowl Environ 2005: tg2-tg2 [Full Text]  
• Lewis, S J G, Foltynie, T, Blackwell, A D, Robbins, T W, Owen, A M, Barker, R A (2005). Heterogeneity of Parkinson's disease in the early clinical stages using a data driven approach. J. Neurol. Neurosurg. Psychiatry 76: 343-348 [Abstract] [Full Text]  
• Lim, K. L., Chew, K. C. M., Tan, J. M. M., Wang, C., Chung, K. K. K., Zhang, Y., Tanaka, Y., Smith, W., Engelender, S., Ross, C. A., Dawson, V. L., Dawson, T. M. (2005). Parkin Mediates Nonclassical, Proteasomal-Independent Ubiquitination of Synphilin-1: Implications for Lewy Body Formation. J. Neurosci. 25: 2002-2009 [Abstract] [Full Text]  
• Yamamoto, A., Friedlein, A., Imai, Y., Takahashi, R., Kahle, P. J., Haass, C. (2005). Parkin Phosphorylation and Modulation of Its E3 Ubiquitin Ligase Activity. J. Biol. Chem. 280: 3390-3399 [Abstract] [Full Text]  
• Wu, R.-M., Bounds, R., Lincoln, S., Hulihan, M., Lin, C.-H., Hwu, W.-L., Chen, J., Gwinn-Hardy, K., Farrer, M. (2005). Parkin Mutations and Early-Onset Parkinsonism in a Taiwanese Cohort. Arch Neurol 62: 82-87 [Abstract] [Full Text]  
• Varrone, A., Pellecchia, M. T., Amboni, M., Sansone, V., Salvatore, E., Ghezzi, D., Garavaglia, B., Brice, A., Brunetti, A., Bonavita, V., De Michele, G., Salvatore, M., Pappata, S., Barone, P. (2004). Imaging of dopaminergic dysfunction with [123I]FP-CIT SPECT in early-onset parkin disease. Neurology 63: 2097-2103 [Abstract] [Full Text]  
• Hatano, Y., Sato, K., Elibol, B., Yoshino, H., Yamamura, Y., Bonifati, V., Shinotoh, H., Asahina, M., Kobayashi, S., Ng, A. R., Rosales, R. L., Hassin-Baer, S., Shinar, Y., Lu, C. S., Chang, H. C., Wu-Chou, Y. H., Atac, F. B., Kobayashi, T., Toda, T., Mizuno, Y., Hattori, N. (2004). PARK6-linked autosomal recessive early-onset parkinsonism in Asian populations. Neurology 63: 1482-1485 [Abstract] [Full Text]  
• Cummings, J. L. (2004). Dementia with Lewy Bodies: Molecular Pathogenesis and Implications for Classification. J Geriatr Psychiatry Neurol 17: 112-119 [Abstract]  
• Sasaki, S., Shirata, A., Yamane, K., Iwata, M. (2004). Parkin-positive autosomal recessive juvenile parkinsonism with {alpha}-synuclein-positive inclusions. Neurology 63: 678-682 [Abstract] [Full Text]  
• von Coelln, R., Thomas, B., Savitt, J. M., Lim, K. L., Sasaki, M., Hess, E. J., Dawson, V. L., Dawson, T. M. (2004). Loss of locus coeruleus neurons and reduced startle in parkin null mice. Proc. Natl. Acad. Sci. USA 101: 10744-10749 [Abstract] [Full Text]  
• West, A. B., Kapatos, G., O'Farrell, C., Gonzalez-de-Chavez, F., Chiu, K., Farrer, M. J., Maidment, N. T. (2004). N-myc Regulates Parkin Expression. J. Biol. Chem. 279: 28896-28902 [Abstract] [Full Text]  
• Scherfler, C., Khan, N. L., Pavese, N., Eunson, L., Graham, E., Lees, A. J., Quinn, N. P., Wood, N. W., Brooks, D. J., Piccini, P. P. (2004). Striatal and cortical pre- and postsynaptic dopaminergic dysfunction in sporadic parkin-linked parkinsonism. Brain 127: 1332-1342 [Abstract] [Full Text]  
• Khan, N. L., Katzenschlager, R., Watt, H., Bhatia, K. P., Wood, N. W., Quinn, N., Lees, A. J. (2004). Olfaction differentiates parkin disease from early-onset parkinsonism and Parkinson disease. Neurology 62: 1224-1226 [Abstract] [Full Text]  
• Mata, I. F., Lockhart, P. J., Farrer, M. J. (2004). Parkin genetics: one model for Parkinson's disease. Hum Mol Genet 13: R127-133 [Abstract] [Full Text]  
• Lockhart, P J, Lincoln, S, Hulihan, M, Kachergus, J, Wilkes, K, Bisceglio, G, Mash, D C, Farrer, M J (2004). DJ-1 mutations are a rare cause of recessively inherited early onset parkinsonism mediated by loss of protein function. J. Med. Genet. 41: e22-22 [Full Text]  
• Foltynie, T., Brayne, C. E. G., Robbins, T. W., Barker, R. A. (2004). The cognitive ability of an incident cohort of Parkinson's patients in the UK. The CamPaIGN study. Brain 127: 550-560 [Abstract] [Full Text]  
• Bandmann, O. (2004). DJ-1: The second gene for early onset Parkinson disease. Neurology 62: 357-358 [Full Text]  
• Hedrich, K., Djarmati, A., Schafer, N., Hering, R., Wellenbrock, C., Weiss, P. H., Hilker, R., Vieregge, P., Ozelius, L. J., Heutink, P., Bonifati, V., Schwinger, E., Lang, A. E., Noth, J., Bressman, S. B., Pramstaller, P. P., Riess, O., Klein, C. (2004). DJ-1 (PARK7) mutations are less frequent than Parkin (PARK2) mutations in early-onset Parkinson disease. Neurology 62: 389-394 [Abstract] [Full Text]  
• Winklhofer, K. F., Henn, I. H., Kay-Jackson, P. C., Heller, U., Tatzelt, J. (2003). Inactivation of Parkin by Oxidative Stress and C-terminal Truncations: A PROTECTIVE ROLE OF MOLECULAR CHAPERONES. J. Biol. Chem. 278: 47199-47208 [Abstract] [Full Text]  
• Cookson, M. R., Lockhart, P. J., McLendon, C., O'Farrell, C., Schlossmacher, M., Farrer, M. J. (2003). RING finger 1 mutations in Parkin produce altered localization of the protein. Hum Mol Genet 12: 2957-2965 [Abstract] [Full Text]  
• Ardley, H. C., Scott, G. B., Rose, S. A., Tan, N. G. S., Markham, A. F., Robinson, P. A. (2003). Inhibition of Proteasomal Activity Causes Inclusion Formation in Neuronal and Non-Neuronal Cells Overexpressing Parkin. Mol. Biol. Cell 14: 4541-4556 [Abstract] [Full Text]  
• Goldberg, M. S., Fleming, S. M., Palacino, J. J., Cepeda, C., Lam, H. A., Bhatnagar, A., Meloni, E. G., Wu, N., Ackerson, L. C., Klapstein, G. J., Gajendiran, M., Roth, B. L., Chesselet, M.-F., Maidment, N. T., Levine, M. S., Shen, J. (2003). Parkin-deficient Mice Exhibit Nigrostriatal Deficits but Not Loss of Dopaminergic Neurons. J. Biol. Chem. 278: 43628-43635 [Abstract] [Full Text]  
• Pankratz, N., Nichols, W. C., Uniacke, S. K., Halter, C., Murrell, J., Rudolph, A., Shults, C. W., Conneally, P. M., Foroud, T., the Parkinson Study Group, (2003). Genome-wide linkage analysis and evidence of gene-by-gene interactions in a sample of 362 multiplex Parkinson disease families. Hum Mol Genet 12: 2599-2608 [Abstract] [Full Text]  
• Zhao, J., Ren, Y., Jiang, Q., Feng, J. (2003). Parkin is recruited to the centrosome in response to inhibition of proteasomes. J. Cell Sci. 116: 4011-4019 [Abstract] [Full Text]  
• Schapira, A.H. V. (2003). Neuroprotection in PD--A role for dopamine agonists?. Neurology 61: S34-42 [Full Text]  
• Itier, J.-M., Ibanez, P., Mena, M. A., Abbas, N., Cohen-Salmon, C., Bohme, G. A., Laville, M., Pratt, J., Corti, O., Pradier, L., Ret, G., Joubert, C., Periquet, M., Araujo, F., Negroni, J., Casarejos, M. J., Canals, S., Solano, R., Serrano, A., Gallego, E., Sanchez, M., Denefle, P., Benavides, J., Tremp, G., Rooney, T. A., Brice, A., Garcia de Yebenes, J. (2003). Parkin gene inactivation alters behaviour and dopamine neurotransmission in the mouse. Hum Mol Genet 12: 2277-2291 [Abstract] [Full Text]  
• Lucking, C.-B., Chesneau, V., Lohmann, E., Verpillat, P., Dulac, C., Bonnet, A.-M., Gasparini, F., Agid, Y., Durr, A., Brice, A. (2003). Coding Polymorphisms in the Parkin Gene and Susceptibility to Parkinson Disease. Arch Neurol 60: 1253-1256 [Abstract] [Full Text]  
• Gray, D. A., Tsirigotis, M., Woulfe, J. (2003). Ubiquitin, Proteasomes, and the Aging Brain. Sci Aging Knowl Environ 2003: re6-6 [Abstract] [Full Text]  
• Dekker, M. C. J., Bonifati, V., van Duijn, C. M. (2003). Parkinson's disease: piecing together a genetic jigsaw. Brain 126: 1722-1733 [Abstract] [Full Text]  
• Tanner, C. M. (2003). PD or not PD?: That is the question. Neurology 61: 5-6 [Full Text]  
• Kahns, S., Kalai, M., Jakobsen, L. D., Clark, B. F. C., Vandenabeele, P., Jensen, P. H. (2003). Caspase-1 and Caspase-8 Cleave and Inactivate Cellular Parkin. J. Biol. Chem. 278: 23376-23380 [Abstract] [Full Text]  
• Marx, F. P., Holzmann, C., Strauss, K. M., Li, L., Eberhardt, O., Gerhardt, E., Cookson, M. R., Hernandez, D., Farrer, M. J., Kachergus, J., Engelender, S., Ross, C. A., Berger, K., Schols, L., Schulz, J. B., Riess, O., Kruger, R. (2003). Identification and functional characterization of a novel R621C mutation in the synphilin-1 gene in Parkinson's disease. Hum Mol Genet 12: 1223-1231 [Abstract] [Full Text]  
• Morrison, K. E. (2003). Parkin mutations and early onset parkinsonism. Brain 126: 1250-1251 [Full Text]  
• Periquet, M., Latouche, M., Lohmann, E., Rawal, N., De Michele, G., Ricard, S., Teive, H., Fraix, V., Vidailhet, M., Nicholl, D., Barone, P., Wood, N. W., Raskin, S., Deleuze, J.-F., Agid, Y., Durr, A., Brice, A. (2003). Parkin mutations are frequent in patients with isolated early-onset parkinsonism. Brain 126: 1271-1278 [Abstract] [Full Text]  
• Khan, N. L., Graham, E., Critchley, P., Schrag, A. E., Wood, N. W., Lees, A. J., Bhatia, K. P., Quinn, N. (2003). Parkin disease: a phenotypic study of a large case series. Brain 126: 1279-1292 [Abstract] [Full Text]  
• Lincoln, S., Wiley, J., Lynch, T., Langston, J. W., Chen, R., Lang, A., Rogaeva, E., Sa, D. S., Munhoz, R. P., Harris, J., Marder, K., Klein, C., Bisceglio, G., Hussey, J., West, A., Hulihan, M., Hardy, J., Farrer, M. (2003). Parkin-proven disease: Common founders but divergent phenotypes. Neurology 60: 1605-1610 [Abstract] [Full Text]  
• Thobois, S., Ribeiro, M.-J., Lohmann, E., Durr, A., Pollak, P., Rascol, O., Guillouet, S., Chapoy, E., Costes, N., Agid, Y., Remy, P., Brice, A., Broussolle, E. (2003). Young-Onset Parkinson Disease With and Without Parkin Gene Mutations: A Fluorodopa F 18 Positron Emission Tomography Study. Arch Neurol 60: 713-718 [Abstract] [Full Text]  
• Zheng, K., Heydari, B., Simon, D. K. (2003). A Common NURR1 Polymorphism Associated With Parkinson Disease and Diffuse Lewy Body Disease. Arch Neurol 60: 722-725 [Abstract] [Full Text]  
• Finney, N., Walther, F., Mantel, P.-Y., Stauffer, D., Rovelli, G., Dev, K. K. (2003). The Cellular Protein Level of Parkin Is Regulated by Its Ubiquitin-like Domain. J. Biol. Chem. 278: 16054-16058 [Abstract] [Full Text]  
• Rawal, N., Periquet, M., Lohmann, E., Lucking, C.B., Teive, H.A., Ambrosio, G., Raskin, S., Lincoln, S., Hattori, N., Guimaraes, J., Horstink, M.W.I.M., Dos Santos Bele, W., Brousolle, E., Destee, A., Mizuno, Y., Farrer, M., Deleuze, J.-F., De Michele, G., Agid, Y., Durr, A., Brice, A. (2003). New parkin mutations and atypical phenotypes in families with autosomal recessive parkinsonism. Neurology 60: 1378-1381 [Abstract] [Full Text]  
• Inzelberg, R., Hattori, N., Nisipeanu, P., Abo Mouch, S., Blumen, S.C., Carasso, R.L., Mizuno, Y. (2003). Camptocormia, axial dystonia, and parkinsonism: Phenotypic heterogeneity of a parkin mutation. Neurology 60: 1393-1394 [Full Text]  
• Ren, Y., Zhao, J., Feng, J. (2003). Parkin Binds to alpha /beta Tubulin and Increases their Ubiquitination and Degradation. J. Neurosci. 23: 3316-3324 [Abstract] [Full Text]  
• Siderowf, A., Stern, M. (2003). Update on Parkinson Disease. ANN INTERN MED 138: 651-658 [Abstract] [Full Text]  
• Nussbaum, R. L., Ellis, C. E. (2003). Alzheimer's Disease and Parkinson's Disease. NEJM 348: 1356-1364 [Full Text]  
• Foroud, T., Uniacke, S.K., Liu, L., Pankratz, N., Rudolph, A., Halter, C., Shults, C., Marder, K., Conneally, P.M., Nichols, W.C., the Parkinson Study Group, (2003). Heterozygosity for a mutation in the parkin gene leads to later onset Parkinson disease. Neurology 60: 796-801 [Abstract] [Full Text]  
• Darios, F., Corti, O., Lucking, C. B., Hampe, C., Muriel, M.-P., Abbas, N., Gu, W.-J., Hirsch, E. C., Rooney, T., Ruberg, M., Brice, A. (2003). Parkin prevents mitochondrial swelling and cytochrome c release in mitochondria-dependent cell death. Hum Mol Genet 12: 517-526 [Abstract] [Full Text]  
• Evans, W. E., McLeod, H. L. (2003). Pharmacogenomics -- Drug Disposition, Drug Targets, and Side Effects. NEJM 348: 538-549 [Full Text]  
• Munoz, E, Tolosa, E, Pastor, P, Marti, M J, Valldeoriola, F, Campdelacreu, J, Oliva, R (2002). Relative high frequency of the c.255delA parkin gene mutation in Spanish patients with autosomal recessive parkinsonism. J. Neurol. Neurosurg. Psychiatry 73: 582-584 [Abstract] [Full Text]  
• Marras, C., Rochon, P., Lang, A. E. (2002). Predicting Motor Decline and Disability in Parkinson Disease: A Systematic Review. Arch Neurol 59: 1724-1728 [Abstract] [Full Text]  
• West, A. B., Maraganore, D., Crook, J., Lesnick, T., Lockhart, P. J., Wilkes, K. M., Kapatos, G., Hardy, J. A., Farrer, M. J. (2002). Functional association of the parkin gene promoter with idiopathic Parkinson's disease. Hum Mol Genet 11: 2787-2792 [Abstract] [Full Text]  
• Foltynie, T, Sawcer, S, Brayne, C, Barker, R A (2002). The genetic basis of Parkinson's disease. J. Neurol. Neurosurg. Psychiatry 73: 363-370 [Abstract] [Full Text]  
• Khan, N. L., Brooks, D. J., Pavese, N., Sweeney, M. G., Wood, N. W., Lees, A. J., Piccini, P. (2002). Progression of nigrostriatal dysfunction in a parkin kindred: an [18F]dopa PET and clinical study. Brain 125: 2248-2256 [Abstract] [Full Text]  
• Nichols, W C, Pankratz, N, Uniacke, S K, Pauciulo, M W, Halter, C, Rudolph, A, Conneally, P M, Foroud, T (2002). Linkage stratification and mutation analysis at the parkin locus identifies mutation positive Parkinson's disease families. J. Med. Genet. 39: 489-492 [Full Text]