Early‐onset familial parkinsonism due to POLG mutations
Abstract
OBJECTIVE: To define the molecular etiology of early-onset parkinsonism and peripheral neuropathy. METHODS: Two sisters had early-onset parkinsonism (dystonic toe curling, action tremor, masked face, bradykinesia, stooped posture, and rigidity), together with clinical and electrophysiological signs of sensorimotor axonal peripheral neuropathy. RESULTS: No mutations were found in the genes for parkin or PINK1. Muscle biopsies showed ragged-red and cytochrome c oxidase-negative fibers, and biochemistry showed decreased activities of respiratory chain complexes containing mitochondrial DNA-encoded subunits. Multiple mitochondrial DNA deletions were seen by long polymerase chain reaction, and sequencing of the POLG gene showed that the patients were compound heterozygous for two patogenic mutations. INTERPRETATION: POLG mutations can cause early-onset parkinsonism in the absence of progressive external ophthalmoplegia.
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Two sisters with early-onset PD, peripheral neuropathy and without PEO had a 37% decrease in mtDNA content with multiple deletions and were found to be compound heterozygous for two missense mutations (G737R and R853W) in Pol γ.
“Two sisters with early-onset PD, peripheral neuropathy and without PEO had a 37% decrease in mtDNA content with multiple deletions and were found to be compound heterozygous for two missense mutations (G737R and R853W) in Pol γ (Davidzon et al., 2006).”
From Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases (2017) · cites this paper as Davidzon et al., 2006
Cites
Molecular Cloning: A Laboratory Manual
Sambrook, J., Fritsch, E., & Maniatis, T. (1989) · UCLA - Biblioteca de Ciencias de la Salud · Cited by 133,589 · see citing works
Hereditary Early-Onset Parkinson's Disease Caused by Mutations in <i>PINK1</i>
Valente, E. M., Abou-Sleiman, P. M., Caputo, V., Muqit, M. M. K., Harvey, K., Gispert, S., Ali, Z., Del Turco, D., Bentivoglio, A. R., Healy, D. G., et al. (2004) · Science · doi:10.1126/science.1096284 · Cited by 3,481 · see citing works
Mitochondria take center stage in aging and neurodegeneration
Beal, M. F. (2005) · Annals of Neurology · doi:10.1002/ana.20624 · Cited by 957 · see citing works
Luoma, P., Melberg, A., Rinne, J. O., Kaukonen, J. A., Nupponen, N. N., Chalmers, R. M., Oldfors, A., Rautakorpi, I., Peltonen, L., Majamaa, K., et al. (2004) · The Lancet · doi:10.1016/s0140-6736(04)16983-3 · Cited by 548 · see citing works
Abbas, N., Lücking, C. B., Ricard, S., Dürr, A., Bonifati, V., Michele, G. D., Bouley, S., Vaughan, J. R., Gasser, T., Marconi, R., et al. (1999) · Human Molecular Genetics · doi:10.1093/hmg/8.4.567 · Cited by 529 · see citing works
Cytochrome c oxidase deficiency in leigh syndrome
DiMauro, S., Servidei, S., Zeviani, M., DiRocco, M., Vivo, D. C. D., DiDonato, S., Uziel, G., Berry, K., Hoganson, G. E., Johnsen, S. D., et al. (1987) · Annals of Neurology · doi:10.1002/ana.410220409 · Cited by 361 · see citing works
Self-citationVyas, I. L., Heikkila, R. E., & Nicklas, W. J. (1986) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1986.tb01768.x · Cited by 242 · see citing works
[43]Cytochemistry and immunocytochemistry of mitochondria in tissue sections
Sciacco, M., & Bonilla, E. (1996) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(96)64045-2 · Cited by 192 · see citing works
Mitochondrial dysfunction in parkinson's disease
Mizuno, Y., Yoshino, H., Ikebe, S.-I., Hattori, N., Kobayashi, T., Shimoda‐Matsubayashi, S., Matsumine, H., & Kondo, T. (1998) · Annals of Neurology · doi:10.1002/ana.410440715 · Cited by 164 · see citing works
Consequences of mutations in human DNA polymerase γ
Longley, M. J., Graziewicz, M. A., Bienstock, R. J., & Copeland, W. C. (2005) · Gene · doi:10.1016/j.gene.2005.03.029 · Cited by 140 · see citing works
Filosto, M., Mancuso, M., Nishigaki, Y., Pancrudo, J., Harati, Y., Gooch, C. L., Mankodi, A. K., Bayne, L. L., Bonilla, E., Shanske, S., et al. (2003) · Archives of Neurology · doi:10.1001/archneur.60.9.1279 · Cited by 118 · see citing works
Self-citationDisorders of nuclear-mitochondrial intergenomic signaling
Spinazzola, A., & Zeviani, M. (2005) · Gene · doi:10.1016/j.gene.2005.03.025 · Cited by 116 · see citing works
Luoma, P. T., Luo, N., Löscher, W. N., Farr, C. L., Horváth, R., Wanschitz, J., Kiechl, S. J., Kaguni, L. S., & Suomalainen, A. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi196 · Cited by 111 · see citing works
Nishigaki, Y. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddh010 · Cited by 101 · see citing works
A Novel Polymerase γ Mutation in a Family With Ophthalmoplegia, Neuropathy, and Parkinsonism
Mancuso, M., Filosto, M., Oh, S. J., & DiMauro, S. (2004) · Archives of Neurology · doi:10.1001/archneur.61.11.1777 · Cited by 92 · see citing works
Self-citationFatal infantile neuromuscular presentation of glycogen storage disease type IV
Tay, S. K. H., Akman, H. O., Chung, W. K., et al. (2004) · Neuromuscular Disorders · doi:10.1016/j.nmd.2003.12.006 · Cited by 73 · see citing works
Mitochondria1 involvement in Parkinson's disease
DiMauro, S. (1993) · Neurology · doi:10.1212/wnl.43.11.2170 · Cited by 51 · see citing works
Self-citationIncreased activity of surviving locus ceruleus neurons in Alzheimer's disease
Moser (1999) · Pure Amsterdam UMC · doi:10.1002/1531-8249(199901)45:1
Correlation of Parkinson's disease severity and duration with123I-FP-CIT SPECT striatal uptake
Benamer, H. T. S., Patterson, J., Wyper, D. J., Hadley, D. M., Macphee, G. J. A., & Grosset, D. G. (2000) · Movement Disorders · doi:10.1002/1531-8257(200007)15:4
Flagged first, then by citations
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Mitochondria in the aetiology and pathogenesis of Parkinson's disease
Schapira, A. H. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(07)70327-7 · Cited by 883 · see citing works
Mitochondrial Defects and Oxidative Stress in Alzheimer Disease and Parkinson Disease
Yan, M. H., Wang, X., & Zhu, X. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.11.014 · Cited by 718 · see citing works
Mitochondrial dysfunction in neurodegenerative disorders
Klemmensen, M. M., Borrowman, S. H., Pearce, C., Pyles, B., & Chandra, B. (2024) · Neurotherapeutics · doi:10.1016/j.neurot.2023.10.002 · Cited by 396 · see citing works
Monzio Compagnoni, G., Di Fonzo, A., Corti, S., Comi, G. P., Bresolin, N., & Masliah, E. (2020) · Molecular Neurobiology · doi:10.1007/s12035-020-01926-1 · Cited by 378 · see citing works
The role of free radicals in the aging brain and Parkinson’s Disease: Convergence and parallelism
Kumar, H., Lim, H.-W., More, S. V., Kim, B.-W., Koppula, S., Kim, I. S., & Choi, D.-K. (2012) · International Journal of Molecular Sciences · doi:10.3390/ijms130810478 · Cited by 212 · see citing works
Gegg, M. E., Cooper, J. M., Schapira, A. H. V., & Taanman, J.-W. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004756 · Cited by 198 · see citing works
DeBalsi, K. L., Hoff, K. E., & Copeland, W. C. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2016.04.006 · Cited by 180 · see citing works
Mitochondrial DNA polymerase gamma variants in idiopathic sporadic Parkinson disease
Luoma, P. T., Eerola, J., Ahola, S., Hakonen, A. H., Hellström, O., Kivistö, K. T., Tienari, P. J., & Suomalainen, A. (2007) · Neurology · doi:10.1212/01.wnl.0000276955.23735.eb · Cited by 154 · see citing works
ccf-mtDNA as a Potential Link Between the Brain and Immune System in Neuro-Immunological Disorders
Gambardella, S., Limanaqi, F., Ferese, R., Biagioni, F., Campopiano, R., Centonze, D., & Fornai, F. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01064 · Cited by 141 · see citing works
The Role of Anti-Inflammatory Agents in Parkinson???s Disease
McGeer, E. G., & McGeer, P. L. (2007) · CNS Drugs · doi:10.2165/00023210-200721100-00001 · Cited by 95 · see citing works
POLG1 in idiopathic Parkinson disease
Tiangyou, W., Hudson, G., Ghezzi, D., Ferrari, G., Zeviani, M., Burn, D. J., & Chinnery, P. F. (2006) · Neurology · doi:10.1212/01.wnl.0000238963.07425.d5 · Cited by 50 · see citing works
H. Swerdlow, R. (2011) · Current Pharmaceutical Design · doi:10.2174/138161211798072535 · Cited by 35 · see citing works
- Authors
- Davidzon, G., Greene, P., Mancuso, M., Klos, K. J., Ahlskog, J. E., Hirano, M., & DiMauro, S.
- Affiliations
- Columbia University Irving Medical Center (US)
- University of Pisa (IT)
- Mayo Clinic (US)
- Corresponding author
- DiMauro, Salvatore
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2006-04-21
- Volume
- 59
- Issue
- 5
- Pages
- 859-862
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2060061148
- Cited by
- 239
- References
- 20
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 4 · 2023: 6 · 2022: 12 · 2021: 12 · 2020: 10 · 2019: 11 · 2018: 12 · 2017: 5 · 2016: 8 · 2015: 12 · 2014: 11 · 2013: 17 · 2012: 13
- FWCI
- 12.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS-11766)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD32062, P01HD032062)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Keywords
- early-onset parkinsonism, POLG mutations, mitochondrial DNA polymerase gamma, familial parkinsonism, peripheral neuropathy, mitochondrial DNA deletions, compound heterozygosity, mitochondrial respiratory chain defects, Parkin, PINK1, chronic progressive external ophthalmoplegia
- MeSH terms
- DNA Polymerase gamma, Adult, Amino Acid Sequence, DNA, DNA-Directed DNA Polymerase, DNA, Mitochondrial, Dystonia, Female, Genes, Recessive, Heterozygote, Humans, Molecular Sequence Data, Mutation, Neuromuscular Diseases, Parkinson Disease, Tremor, Ophthalmoplegia, Chronic Progressive External, Age of Onset, Muscle, Skeletal
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