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Entry
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- #556500 - PARKINSON DISEASE, MITOCHONDRIAL
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- OMIM
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<span class="text-danger"><strong>#</strong></span>
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556500
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<p>A number sign (#) is used with this entry because, as reviewed in <a href="/entry/168600">168600</a>, parkinsonism is a conspicuous and even predominant feature of some of the various neurologic disorders and, as reviewed here, mitochondrial mutations may be involved.</p><p>The electron transport chain (ETC) of mitochondria is the last step in cellular respiration. The ETC composes the primary mechanism by which electrons are conferred to oxygen for the production of adenosine triphosphate (ATP), a major energy supplying molecule in all cells. The ETC is composed of five transmembrane (spanning the inner mitochondrial membrane) complexes, 4 of which have subunits coded for by mitochondrial and nuclear DNA, 1 of which has subunits coded for by nuclear DNA only. Complexes I, II, III, and IV transport electrons to oxygen and pump protons into the space between the two mitochondrial membranes. Complex V uses the proton gradient to generate ATP. Reactive oxygen species (ROS), molecules that cause damage to existing cellular structures as well as DNA, are created by the activities of the ETC. As a result, abnormal complex activity can lead to an excess of ROS and potential mitochondrial damage.</p><p>As reviewed by <a href="#1" class="mim-tip-reference" title="Di Monte, D. A. <strong>Mitochondrial DNA and Parkinson's disease.</strong> Neurology 41 (suppl. 2): 38-42, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1904141/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1904141</a>] [<a href="https://doi.org/10.1212/wnl.41.5_suppl_2.38" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1904141">Di Monte (1991)</a>, the first suggestion that a mitochondrial defect may be involved in the neuronal death observed in Parkinson disease stems from studies on the mechanism of neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Death of dopaminergic neurons of the substantia nigra after exposure to MPTP is due to the fact that this neurotoxicant is oxidized in the CNS by monoamine oxidase (MAO) type B, generating a metabolite that is the ultimate mediator of MPTP toxicity. Pretreatment of animals with MAO inhibitors protected against the neurotoxic effects of MPTP. In some studies a reduction of complex I activity was found in autopsy specimens of the substantia nigra of patients affected by Parkinson disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1904141" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The low concordance of the disease among twins and the reports that prevalence is similar in identical and fraternal twins (<a href="#2" class="mim-tip-reference" title="Duvoisin, R. C. <strong>Genetics of Parkinson's disease.</strong> Adv. Neurol. 45: 307-312, 1986."None>Duvoisin, 1986</a>; <a href="#6" class="mim-tip-reference" title="Marttila, R. J., Kaprio, J., Koskenvuo, M., Rinne, U. K. <strong>Parkinson's disease in a nationwide twin cohort.</strong> Neurology 38: 1217-1219, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3399070/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3399070</a>] [<a href="https://doi.org/10.1212/wnl.38.8.1217" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3399070">Marttila et al., 1988</a>) could be explained by mitochondrial inheritance; different mitochondrial phenotypes in monozygotic twins can occur because of random segregation of heteroplasmic mitochondrial DNA from the ovum. To test the mitochondrial hypothesis, <a href="#17" class="mim-tip-reference" title="Zweig, R. M., Singh, A., Cardiollo, J. E., Langston, J. W. <strong>The familial occurrence of Parkinson's disease: lack of evidence for maternal inheritance.</strong> Arch. Neurol. 49: 1205-1207, 1992. Note: Erratum: Arch. Neurol. 50: 153 only, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1288529/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1288529</a>] [<a href="https://doi.org/10.1001/archneur.1992.00530350127029" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1288529">Zweig et al. (1992)</a> questioned the occurrence of Parkinson disease in the parents of 252 patients. It was found that 11 fathers and 5 mothers had had this disease. These data failed to provide support for the hypothesis of maternal inheritance. In a review of similar studies in the literature and an additional unpublished study, <a href="#17" class="mim-tip-reference" title="Zweig, R. M., Singh, A., Cardiollo, J. E., Langston, J. W. <strong>The familial occurrence of Parkinson's disease: lack of evidence for maternal inheritance.</strong> Arch. Neurol. 49: 1205-1207, 1992. Note: Erratum: Arch. Neurol. 50: 153 only, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1288529/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1288529</a>] [<a href="https://doi.org/10.1001/archneur.1992.00530350127029" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1288529">Zweig et al. (1992)</a> found 922 patients with this disease among whose parents 37 fathers and 19 mothers were reportedly affected. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3399070+1288529" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Parker, W. D., Jr., Boyson, S. J., Parks, J. K. <strong>Abnormalities of the electron transport chain in idiopathic Parkinson's disease.</strong> Ann. Neurol. 26: 719-723, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2557792/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2557792</a>] [<a href="https://doi.org/10.1002/ana.410260606" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2557792">Parker et al. (1989)</a>, using platelet mitochondria from 10 patients with idiopathic Parkinson disease (PD), evaluated catalytic activities for complex I (NADH:ubiquinone oxidoreductase) and complex IV (succinate:cytochrome c oxidoreductase) activity. They found in all ten patients significant reduction of complex I activity and nonsignificant reduction of complex IV activity, suggesting that defects in complex I may explain the pathogenesis of PD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2557792" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Mizuno, Y., Ohta, S., Tanaka, M., Takamiya, S., Suzuki, K., Sato, T., Oya, H., Ozawa, T., Kagawa, Y. <strong>Deficiencies in complex I subunits of the respiratory chain in Parkinson's disease.</strong> Biochem. Biophys. Res. Commun. 163: 1450-1455, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2551290/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2551290</a>] [<a href="https://doi.org/10.1016/0006-291x(89)91141-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2551290">Mizuno et al. (1989)</a>, using mitochondria from striata of patients who died of PD, performed immunoblotting studies to assess the amount present of each subunit of complexes I, III, and IV. They found that 3 of 7 subunits of complex I coded for by the mitochondrial genome were present in lower amounts than those of control mitochondria. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2551290" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Shoffner, J. M., Watts, R. L., Juncos, J. L., Torroni, A., Wallace, D. C. <strong>Mitochondrial oxidative phosphorylation defects in Parkinson's disease.</strong> Ann. Neurol. 30: 332-339, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1952821/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1952821</a>] [<a href="https://doi.org/10.1002/ana.410300304" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1952821">Shoffner et al. (1991)</a>, using skeletal muscle mitochondria from six patients with PD, performed functional assays for all five ETC complexes and looked for mutations in the mitochondrial DNA. The advantage to muscle mitochondria for these studies was the low complex I activity in platelets, the loss of neurons in the substantia nigra of patients with PD, and the more extensive experience with oxidative phosphorylation enzymology in skeletal muscle compared to platelets or neurons. In 4 patients, a decrease in complex I activity was observed. In 1 patient, a decrease in complex IV activity was found. In one patient, no decreases in activity of any complex were found. No known pathological mitochondrial DNA insertion-deletions or point mutations were found. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1952821" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Ikebe, S., Tanaka, M., Ozawa, T. <strong>Point mutations of mitochondrial genome in Parkinson's disease.</strong> Molec. Brain Res. 28: 281-295, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7723627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7723627</a>] [<a href="https://doi.org/10.1016/0169-328x(94)00209-w" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7723627">Ikebe et al. (1995)</a> examined mitochondrial DNA from five patients with PD to locate possible mutations. While no recognized point mutations were found, each patient had multiple point mutations that would cause significant changes to products of genes. Each patient had at least one significant point mutation in genes encoding subunits of complex I. The authors suggested that these changes may lead to the increase of or increased susceptibility to damage from oxygen radicals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7723627" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Swerdlow, R. H., Parks, J. K., Miller, S. W., Tuttle, J. B., Trimmer, P. A., Sheehan, J. P., Bennett, J. P., Jr., Davis, R. E., Parker, W. D., Jr. <strong>Origin and functional consequences of the complex I defect in Parkinson's disease.</strong> Ann. Neurol. 40: 663-671, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8871587/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8871587</a>] [<a href="https://doi.org/10.1002/ana.410400417" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8871587">Swerdlow et al. (1996)</a> used a cybrid cell fusion to repopulate human neuroblastoma cells that had had their mitochondria inactivated with platelet derived mitochondria of patients with idiopathic PD. The cells were assessed for ETC activities, production of ROS, and sensitivity to apoptotic cell death as induced by 1-methyl-4-phenylpyridinium (MPP+), a known inhibitor of complex I. The cybrid technique removes the possibility that ETC assays for activity may not be assessing flaws inherent to ETC complexes rather but toxins or medicines present in the cells of patients with PD. A 20% decrease in complex I activity was seen in the neuroblastoma cell cultures after 5 to 6 weeks of cell division. No significant decrease in complex IV activity was seen. An increase in the production of ROS was seen. Increased susceptibility to MPP+-induced apoptosis was seen. The authors concluded that the complex I defect in PD appeared to arise genetically from mitochondrial DNA, a significant conclusion towards the etiology and pathology of PD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8871587" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The possibility of mitochondrial dysfunction as the basis of idiopathic Parkinson disease has been particularly attractive since <a href="#16" class="mim-tip-reference" title="Vyas, I., Heikkila, R. E., Nicklas, W. J. <strong>Studies on the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: inhibition of NAD-linked substrate oxidation by its metabolite, 1-methyl-4-phenylpyridinium.</strong> J. Neurochem. 46: 1501-1507, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3485701/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3485701</a>] [<a href="https://doi.org/10.1111/j.1471-4159.1986.tb01768.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3485701">Vyas et al. (1986)</a> recognized that the parkinsonism-inducing compound N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a mitochondrial toxin. <a href="#9" class="mim-tip-reference" title="Parker, W. D., Jr., Swerdlow, R. H. <strong>Mitochondrial dysfunction in idiopathic Parkinson disease.</strong> Am. J. Hum. Genet. 62: 758-762, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9529370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9529370</a>] [<a href="https://doi.org/10.1086/301812" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9529370">Parker and Swerdlow (1998)</a> pointed out that the unique genetic properties of mitochondria also make them worthy of consideration for a pathogenic role in PD. Although affected persons occasionally provide family histories that suggest mendelian inheritance and mutations in the gene encoding alpha-synuclein, SNCA (<a href="/entry/163890">163890</a>), have been described in autosomal dominant Parkinson disease, most cases are sporadic. Because of unique features such as heteroplasmy, replicative segregation, and threshold effects, mitochondrial inheritance can allow for the apparent sporadic nature of these diseases. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9529370+3485701" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>To test the hypothesis that mitochondrial variation contributes to expression, <a href="#15" class="mim-tip-reference" title="van der Walt, J. M., Nicodemus, K. K., Martin, E. R., Scott, W. K., Nance, M. A., Watts, R. L., Hubble, J. P., Haines, J. L., Koller, W. C., Lyons, K., Pahwa, R., Stern, M. B., and 15 others. <strong>Mitochondrial polymorphisms significantly reduce the risk of Parkinson disease.</strong> Am. J. Hum. Genet. 72: 804-811, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12618962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12618962</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12618962[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/373937" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12618962">van der Walt et al. (2003)</a> genotyped 10 single-nucleotide polymorphisms that define the European mitochondrial DNA haplogroups in 609 white patients with PD and 340 unaffected white control subjects. Overall, individuals classified as haplogroup J (odds ratio = 0.55; 95% CI 0.91; P = 0.02) or K (odds ratio = 0.52; 95% CI 0.30-0.90; P = 0.02) demonstrated a significant decrease in risk of PD versus individuals carrying the most common haplogroup H. Furthermore, a specific SNP that defines these 2 haplogroups, 10398G, is strongly associated with this protective effect (odds ratio = 0.53; 95% CI 0.39-0.73; P = 0.0001). The 10398G SNP causes a nonconservative amino acid change from threonine to alanine within the NADH dehydrogenase 3 (ND3; <a href="/entry/516002">516002</a>) of complex I. After stratification by sex, this decrease in risk appeared stronger in women than in men. In addition, the 9055A SNP of ATP6 (<a href="/entry/516060">516060</a>) demonstrated a protective effect for women. <a href="#15" class="mim-tip-reference" title="van der Walt, J. M., Nicodemus, K. K., Martin, E. R., Scott, W. K., Nance, M. A., Watts, R. L., Hubble, J. P., Haines, J. L., Koller, W. C., Lyons, K., Pahwa, R., Stern, M. B., and 15 others. <strong>Mitochondrial polymorphisms significantly reduce the risk of Parkinson disease.</strong> Am. J. Hum. Genet. 72: 804-811, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12618962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12618962</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12618962[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/373937" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12618962">Van der Walt et al. (2003)</a> concluded that ND3 may be an important factor in PD susceptibility among white individuals and could help explain the role of complex I in Parkinson disease expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12618962" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By haplotype analysis of 455 patients with PD, 185 patients with Alzheimer disease (AD; <a href="/entry/104300">104300</a>), and 447 controls, <a href="#11" class="mim-tip-reference" title="Pyle, A., Foltynie, T., Tiangyou, W., Lambert, C., Keers, S. M., Allcock, L. M., Davison, J., Lewis, S. J., Perry, R. H., Barker, R., Burn, D. J., Chinnery, P. F. <strong>Mitochondrial DNA haplogroup cluster UKJT reduces the risk of PD.</strong> Ann. Neurol. 57: 564-567, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15786469/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15786469</a>] [<a href="https://doi.org/10.1002/ana.20417" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15786469">Pyle et al. (2005)</a> found that the UKJT haplotype cluster (<a href="#14" class="mim-tip-reference" title="Torroni, A., Huoponen, K., Francalacci, P., Petrozzi, M., Morelli, L., Scozzari, R., Obinu, D., Savontaus, M.-L., Wallace, D. C. <strong>Classification of European mtDNAs from an analysis of three European populations.</strong> Genetics 144: 1835-1850, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8978068/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8978068</a>] [<a href="https://doi.org/10.1093/genetics/144.4.1835" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8978068">Torroni et al., 1996</a>) was associated with a 22% reduction in risk for development of PD. There was no association between any haplotypes and AD, indicating that the association was specific for Parkinson disease. Reanalysis of the data reported by <a href="#15" class="mim-tip-reference" title="van der Walt, J. M., Nicodemus, K. K., Martin, E. R., Scott, W. K., Nance, M. A., Watts, R. L., Hubble, J. P., Haines, J. L., Koller, W. C., Lyons, K., Pahwa, R., Stern, M. B., and 15 others. <strong>Mitochondrial polymorphisms significantly reduce the risk of Parkinson disease.</strong> Am. J. Hum. Genet. 72: 804-811, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12618962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12618962</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12618962[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/373937" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12618962">van der Walt et al. (2003)</a> showed similar results for the pooled data of haplotypes U, K, J, and T. <a href="#11" class="mim-tip-reference" title="Pyle, A., Foltynie, T., Tiangyou, W., Lambert, C., Keers, S. M., Allcock, L. M., Davison, J., Lewis, S. J., Perry, R. H., Barker, R., Burn, D. J., Chinnery, P. F. <strong>Mitochondrial DNA haplogroup cluster UKJT reduces the risk of PD.</strong> Ann. Neurol. 57: 564-567, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15786469/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15786469</a>] [<a href="https://doi.org/10.1002/ana.20417" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15786469">Pyle et al. (2005)</a> noted that the 10398A-G polymorphism has been described on several other haplotypes (see <a href="#3" class="mim-tip-reference" title="Herrnstadt, C., Elson, J. L., Fahy, E., Preston, G., Turnbull, D. M., Anderson, C., Ghosh, S. S., Olefsky, J. M., Beal, M. F., Davis, R. E., Howell, N. <strong>Reduced-median-network analysis of complete mitochondrial DNA coding-region sequences for the major African, Asian, and European haplogroups.</strong> Am. J. Hum. Genet. 70: 1152-1171, 2002. Note: Erratum: Am. J. Hum. Genet. 71: 448 only, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11938495/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11938495</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11938495[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/339933" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11938495">Herrnstadt et al., 2002</a>), indicating that the 10398A-G polymorphism does not 'define' haplotypes J and K, as asserted by <a href="#15" class="mim-tip-reference" title="van der Walt, J. M., Nicodemus, K. K., Martin, E. R., Scott, W. K., Nance, M. A., Watts, R. L., Hubble, J. P., Haines, J. L., Koller, W. C., Lyons, K., Pahwa, R., Stern, M. B., and 15 others. <strong>Mitochondrial polymorphisms significantly reduce the risk of Parkinson disease.</strong> Am. J. Hum. Genet. 72: 804-811, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12618962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12618962</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12618962[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/373937" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12618962">van der Walt et al. (2003)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15786469+8978068+12618962+11938495" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Horvath, R., Kley, R. A., Lochmuller, H., Vorgerd, M. <strong>Parkinson syndrome, neuropathy, and myopathy caused by the mutation A8344G (MERRF) in tRNA-lys.</strong> Neurology 68: 56-58, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17200493/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17200493</a>] [<a href="https://doi.org/10.1212/01.wnl.0000250334.48038.7a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17200493">Horvath et al. (2007)</a> reported a 66-year-old German man with parkinsonism due to an 8344A-G mutation in the MTTK gene (<a href="/entry/590060#0001">590060.0001</a>). Symptoms included bradykinesia, resting tremor, and asymmetric rigidity. He also had proximal muscle weakness, hyporeflexia, decreased distal sensation, and bilateral hearing loss. Serum creatine kinase was elevated. He showed good response to levodopa. Skeletal muscle biopsy showed ragged-red fibers, fiber size variability, centrally placed nuclei, and atrophic and necrotic fibers. There was a mild decrease in some respiratory chain enzymes. The 8344A-G mutation was homoplasmic in muscle and 80% in leukocytes. A brother with progressive hearing loss since age 10 had 70% heteroplasmy in blood. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17200493" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a patient with early-onset Parkinson disease (PARK6; <a href="/entry/605909">605909</a>) due to homozygous mutation in the PINK1 gene (<a href="/entry/608309#0002">608309.0002</a>), <a href="#10" class="mim-tip-reference" title="Piccoli, C., Ripoli, M., Quarato, G., Scrima, R., D'Aprile, A., Boffoli, D., Margaglione, M., Criscuolo, C., De Michele, G., Sardanelli, A., Papa, S., Capitanio, N. <strong>Coexistence of mutations in PINK1 and mitochondrial DNA in early onset parkinsonism. (Letter)</strong> J. Med. Genet. 45: 596-602, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18524835/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18524835</a>] [<a href="https://doi.org/10.1136/jmg.2008.058628" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18524835">Piccoli et al. (2008)</a> identified homoplasmic mutations in the MTND5 (<a href="/entry/516005#0010">516005.0010</a>) and MTND6 genes (<a href="/entry/516006#0008">516006.0008</a>), respectively. The patient had onset at age 22 years. His mother, who was heterozygous for the PINK1 mutation, was also homoplasmic for both mitochondrial mutations and showed disease onset at age 53. The father was heterozygous for the PINK1 mutation only and was unaffected at age 79. Biochemical studies of the proband's fibroblasts showed mitochondrial dysfunction, with decreased amounts of cytochrome c oxidase, impaired complex I activity, and increased hydrogen peroxide generation. <a href="#10" class="mim-tip-reference" title="Piccoli, C., Ripoli, M., Quarato, G., Scrima, R., D'Aprile, A., Boffoli, D., Margaglione, M., Criscuolo, C., De Michele, G., Sardanelli, A., Papa, S., Capitanio, N. <strong>Coexistence of mutations in PINK1 and mitochondrial DNA in early onset parkinsonism. (Letter)</strong> J. Med. Genet. 45: 596-602, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18524835/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18524835</a>] [<a href="https://doi.org/10.1136/jmg.2008.058628" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18524835">Piccoli et al. (2008)</a> concluded that the presence of the mitochondrial mutations in combination with the PINK1 mutation may have accelerated the onset of the disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18524835" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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</span>
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</div>
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<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
|
|
<ol>
|
|
|
|
<li>
|
|
<a id="1" class="mim-anchor"></a>
|
|
<a id="Di Monte1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Di Monte, D. A.
|
|
<strong>Mitochondrial DNA and Parkinson's disease.</strong>
|
|
Neurology 41 (suppl. 2): 38-42, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1904141/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1904141</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1904141" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/wnl.41.5_suppl_2.38" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Duvoisin1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Duvoisin, R. C.
|
|
<strong>Genetics of Parkinson's disease.</strong>
|
|
Adv. Neurol. 45: 307-312, 1986.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Herrnstadt2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Herrnstadt, C., Elson, J. L., Fahy, E., Preston, G., Turnbull, D. M., Anderson, C., Ghosh, S. S., Olefsky, J. M., Beal, M. F., Davis, R. E., Howell, N.
|
|
<strong>Reduced-median-network analysis of complete mitochondrial DNA coding-region sequences for the major African, Asian, and European haplogroups.</strong>
|
|
Am. J. Hum. Genet. 70: 1152-1171, 2002. Note: Erratum: Am. J. Hum. Genet. 71: 448 only, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11938495/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11938495</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11938495[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11938495" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/339933" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Horvath2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Horvath, R., Kley, R. A., Lochmuller, H., Vorgerd, M.
|
|
<strong>Parkinson syndrome, neuropathy, and myopathy caused by the mutation A8344G (MERRF) in tRNA-lys.</strong>
|
|
Neurology 68: 56-58, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17200493/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17200493</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17200493" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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|
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[<a href="https://doi.org/10.1212/01.wnl.0000250334.48038.7a" target="_blank">Full Text</a>]
|
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|
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</p>
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Ikebe1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ikebe, S., Tanaka, M., Ozawa, T.
|
|
<strong>Point mutations of mitochondrial genome in Parkinson's disease.</strong>
|
|
Molec. Brain Res. 28: 281-295, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7723627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7723627</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7723627" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0169-328x(94)00209-w" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Marttila1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Marttila, R. J., Kaprio, J., Koskenvuo, M., Rinne, U. K.
|
|
<strong>Parkinson's disease in a nationwide twin cohort.</strong>
|
|
Neurology 38: 1217-1219, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3399070/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3399070</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3399070" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
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[<a href="https://doi.org/10.1212/wnl.38.8.1217" target="_blank">Full Text</a>]
|
|
|
|
|
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</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Mizuno1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mizuno, Y., Ohta, S., Tanaka, M., Takamiya, S., Suzuki, K., Sato, T., Oya, H., Ozawa, T., Kagawa, Y.
|
|
<strong>Deficiencies in complex I subunits of the respiratory chain in Parkinson's disease.</strong>
|
|
Biochem. Biophys. Res. Commun. 163: 1450-1455, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2551290/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2551290</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2551290" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0006-291x(89)91141-8" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Parker1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Parker, W. D., Jr., Boyson, S. J., Parks, J. K.
|
|
<strong>Abnormalities of the electron transport chain in idiopathic Parkinson's disease.</strong>
|
|
Ann. Neurol. 26: 719-723, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2557792/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2557792</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2557792" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ana.410260606" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Parker1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Parker, W. D., Jr., Swerdlow, R. H.
|
|
<strong>Mitochondrial dysfunction in idiopathic Parkinson disease.</strong>
|
|
Am. J. Hum. Genet. 62: 758-762, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9529370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9529370</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9529370" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
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|
|
|
[<a href="https://doi.org/10.1086/301812" target="_blank">Full Text</a>]
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|
|
|
|
|
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|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
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<a id="Piccoli2008" class="mim-anchor"></a>
|
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Piccoli, C., Ripoli, M., Quarato, G., Scrima, R., D'Aprile, A., Boffoli, D., Margaglione, M., Criscuolo, C., De Michele, G., Sardanelli, A., Papa, S., Capitanio, N.
|
|
<strong>Coexistence of mutations in PINK1 and mitochondrial DNA in early onset parkinsonism. (Letter)</strong>
|
|
J. Med. Genet. 45: 596-602, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18524835/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18524835</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18524835" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1136/jmg.2008.058628" target="_blank">Full Text</a>]
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|
|
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<li>
|
|
<a id="11" class="mim-anchor"></a>
|
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<a id="Pyle2005" class="mim-anchor"></a>
|
|
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|
|
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|
|
Pyle, A., Foltynie, T., Tiangyou, W., Lambert, C., Keers, S. M., Allcock, L. M., Davison, J., Lewis, S. J., Perry, R. H., Barker, R., Burn, D. J., Chinnery, P. F.
|
|
<strong>Mitochondrial DNA haplogroup cluster UKJT reduces the risk of PD.</strong>
|
|
Ann. Neurol. 57: 564-567, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15786469/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15786469</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15786469" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1002/ana.20417" target="_blank">Full Text</a>]
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|
|
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|
|
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<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Shoffner1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shoffner, J. M., Watts, R. L., Juncos, J. L., Torroni, A., Wallace, D. C.
|
|
<strong>Mitochondrial oxidative phosphorylation defects in Parkinson's disease.</strong>
|
|
Ann. Neurol. 30: 332-339, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1952821/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1952821</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1952821" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
|
|
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[<a href="https://doi.org/10.1002/ana.410300304" target="_blank">Full Text</a>]
|
|
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|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
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<a id="Swerdlow1996" class="mim-anchor"></a>
|
|
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|
|
<p class="mim-text-font">
|
|
Swerdlow, R. H., Parks, J. K., Miller, S. W., Tuttle, J. B., Trimmer, P. A., Sheehan, J. P., Bennett, J. P., Jr., Davis, R. E., Parker, W. D., Jr.
|
|
<strong>Origin and functional consequences of the complex I defect in Parkinson's disease.</strong>
|
|
Ann. Neurol. 40: 663-671, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8871587/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8871587</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8871587" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
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[<a href="https://doi.org/10.1002/ana.410400417" target="_blank">Full Text</a>]
|
|
|
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|
|
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|
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|
|
</li>
|
|
|
|
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|
|
<a id="14" class="mim-anchor"></a>
|
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<a id="Torroni1996" class="mim-anchor"></a>
|
|
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|
|
<p class="mim-text-font">
|
|
Torroni, A., Huoponen, K., Francalacci, P., Petrozzi, M., Morelli, L., Scozzari, R., Obinu, D., Savontaus, M.-L., Wallace, D. C.
|
|
<strong>Classification of European mtDNAs from an analysis of three European populations.</strong>
|
|
Genetics 144: 1835-1850, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8978068/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8978068</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8978068" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/genetics/144.4.1835" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="van der Walt2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
van der Walt, J. M., Nicodemus, K. K., Martin, E. R., Scott, W. K., Nance, M. A., Watts, R. L., Hubble, J. P., Haines, J. L., Koller, W. C., Lyons, K., Pahwa, R., Stern, M. B., and 15 others.
|
|
<strong>Mitochondrial polymorphisms significantly reduce the risk of Parkinson disease.</strong>
|
|
Am. J. Hum. Genet. 72: 804-811, 2003.
|
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12618962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12618962</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12618962[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12618962" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1086/373937" target="_blank">Full Text</a>]
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Vyas, I., Heikkila, R. E., Nicklas, W. J.
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<strong>Studies on the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: inhibition of NAD-linked substrate oxidation by its metabolite, 1-methyl-4-phenylpyridinium.</strong>
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J. Neurochem. 46: 1501-1507, 1986.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3485701/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3485701</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3485701" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1471-4159.1986.tb01768.x" target="_blank">Full Text</a>]
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Zweig, R. M., Singh, A., Cardiollo, J. E., Langston, J. W.
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<strong>The familial occurrence of Parkinson's disease: lack of evidence for maternal inheritance.</strong>
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Arch. Neurol. 49: 1205-1207, 1992. Note: Erratum: Arch. Neurol. 50: 153 only, 1993.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1288529/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1288529</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1288529" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1001/archneur.1992.00530350127029" target="_blank">Full Text</a>]
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Cassandra L. Kniffin - updated : 10/6/2008
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Cassandra L. Kniffin - updated : 2/4/2008<br>Cassandra L. Kniffin - updated : 6/29/2005<br>Ada Hamosh - updated : 5/9/2003<br>Victor A. McKusick - updated : 5/14/1998<br>James R. Poush - updated : 12/19/1996
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Victor A. McKusick : 3/1/1993
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alopez : 09/23/2016
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terry : 07/06/2012<br>terry : 6/7/2012<br>carol : 12/10/2008<br>wwang : 10/7/2008<br>ckniffin : 10/6/2008<br>wwang : 9/8/2008<br>wwang : 2/19/2008<br>ckniffin : 2/4/2008<br>ckniffin : 8/30/2005<br>carol : 7/14/2005<br>ckniffin : 6/29/2005<br>cwells : 5/12/2003<br>terry : 5/9/2003<br>dholmes : 7/2/1998<br>dholmes : 7/2/1998<br>alopez : 5/19/1998<br>terry : 5/14/1998<br>terry : 8/5/1997<br>alopez : 6/9/1997<br>jamie : 12/19/1996<br>mark : 9/13/1995<br>carol : 3/1/1993
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<p>A number sign (#) is used with this entry because, as reviewed in 168600, parkinsonism is a conspicuous and even predominant feature of some of the various neurologic disorders and, as reviewed here, mitochondrial mutations may be involved.</p><p>The electron transport chain (ETC) of mitochondria is the last step in cellular respiration. The ETC composes the primary mechanism by which electrons are conferred to oxygen for the production of adenosine triphosphate (ATP), a major energy supplying molecule in all cells. The ETC is composed of five transmembrane (spanning the inner mitochondrial membrane) complexes, 4 of which have subunits coded for by mitochondrial and nuclear DNA, 1 of which has subunits coded for by nuclear DNA only. Complexes I, II, III, and IV transport electrons to oxygen and pump protons into the space between the two mitochondrial membranes. Complex V uses the proton gradient to generate ATP. Reactive oxygen species (ROS), molecules that cause damage to existing cellular structures as well as DNA, are created by the activities of the ETC. As a result, abnormal complex activity can lead to an excess of ROS and potential mitochondrial damage.</p><p>As reviewed by Di Monte (1991), the first suggestion that a mitochondrial defect may be involved in the neuronal death observed in Parkinson disease stems from studies on the mechanism of neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Death of dopaminergic neurons of the substantia nigra after exposure to MPTP is due to the fact that this neurotoxicant is oxidized in the CNS by monoamine oxidase (MAO) type B, generating a metabolite that is the ultimate mediator of MPTP toxicity. Pretreatment of animals with MAO inhibitors protected against the neurotoxic effects of MPTP. In some studies a reduction of complex I activity was found in autopsy specimens of the substantia nigra of patients affected by Parkinson disease. </p><p>The low concordance of the disease among twins and the reports that prevalence is similar in identical and fraternal twins (Duvoisin, 1986; Marttila et al., 1988) could be explained by mitochondrial inheritance; different mitochondrial phenotypes in monozygotic twins can occur because of random segregation of heteroplasmic mitochondrial DNA from the ovum. To test the mitochondrial hypothesis, Zweig et al. (1992) questioned the occurrence of Parkinson disease in the parents of 252 patients. It was found that 11 fathers and 5 mothers had had this disease. These data failed to provide support for the hypothesis of maternal inheritance. In a review of similar studies in the literature and an additional unpublished study, Zweig et al. (1992) found 922 patients with this disease among whose parents 37 fathers and 19 mothers were reportedly affected. </p><p>Parker et al. (1989), using platelet mitochondria from 10 patients with idiopathic Parkinson disease (PD), evaluated catalytic activities for complex I (NADH:ubiquinone oxidoreductase) and complex IV (succinate:cytochrome c oxidoreductase) activity. They found in all ten patients significant reduction of complex I activity and nonsignificant reduction of complex IV activity, suggesting that defects in complex I may explain the pathogenesis of PD. </p><p>Mizuno et al. (1989), using mitochondria from striata of patients who died of PD, performed immunoblotting studies to assess the amount present of each subunit of complexes I, III, and IV. They found that 3 of 7 subunits of complex I coded for by the mitochondrial genome were present in lower amounts than those of control mitochondria. </p><p>Shoffner et al. (1991), using skeletal muscle mitochondria from six patients with PD, performed functional assays for all five ETC complexes and looked for mutations in the mitochondrial DNA. The advantage to muscle mitochondria for these studies was the low complex I activity in platelets, the loss of neurons in the substantia nigra of patients with PD, and the more extensive experience with oxidative phosphorylation enzymology in skeletal muscle compared to platelets or neurons. In 4 patients, a decrease in complex I activity was observed. In 1 patient, a decrease in complex IV activity was found. In one patient, no decreases in activity of any complex were found. No known pathological mitochondrial DNA insertion-deletions or point mutations were found. </p><p>Ikebe et al. (1995) examined mitochondrial DNA from five patients with PD to locate possible mutations. While no recognized point mutations were found, each patient had multiple point mutations that would cause significant changes to products of genes. Each patient had at least one significant point mutation in genes encoding subunits of complex I. The authors suggested that these changes may lead to the increase of or increased susceptibility to damage from oxygen radicals. </p><p>Swerdlow et al. (1996) used a cybrid cell fusion to repopulate human neuroblastoma cells that had had their mitochondria inactivated with platelet derived mitochondria of patients with idiopathic PD. The cells were assessed for ETC activities, production of ROS, and sensitivity to apoptotic cell death as induced by 1-methyl-4-phenylpyridinium (MPP+), a known inhibitor of complex I. The cybrid technique removes the possibility that ETC assays for activity may not be assessing flaws inherent to ETC complexes rather but toxins or medicines present in the cells of patients with PD. A 20% decrease in complex I activity was seen in the neuroblastoma cell cultures after 5 to 6 weeks of cell division. No significant decrease in complex IV activity was seen. An increase in the production of ROS was seen. Increased susceptibility to MPP+-induced apoptosis was seen. The authors concluded that the complex I defect in PD appeared to arise genetically from mitochondrial DNA, a significant conclusion towards the etiology and pathology of PD. </p><p>The possibility of mitochondrial dysfunction as the basis of idiopathic Parkinson disease has been particularly attractive since Vyas et al. (1986) recognized that the parkinsonism-inducing compound N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a mitochondrial toxin. Parker and Swerdlow (1998) pointed out that the unique genetic properties of mitochondria also make them worthy of consideration for a pathogenic role in PD. Although affected persons occasionally provide family histories that suggest mendelian inheritance and mutations in the gene encoding alpha-synuclein, SNCA (163890), have been described in autosomal dominant Parkinson disease, most cases are sporadic. Because of unique features such as heteroplasmy, replicative segregation, and threshold effects, mitochondrial inheritance can allow for the apparent sporadic nature of these diseases. </p><p>To test the hypothesis that mitochondrial variation contributes to expression, van der Walt et al. (2003) genotyped 10 single-nucleotide polymorphisms that define the European mitochondrial DNA haplogroups in 609 white patients with PD and 340 unaffected white control subjects. Overall, individuals classified as haplogroup J (odds ratio = 0.55; 95% CI 0.91; P = 0.02) or K (odds ratio = 0.52; 95% CI 0.30-0.90; P = 0.02) demonstrated a significant decrease in risk of PD versus individuals carrying the most common haplogroup H. Furthermore, a specific SNP that defines these 2 haplogroups, 10398G, is strongly associated with this protective effect (odds ratio = 0.53; 95% CI 0.39-0.73; P = 0.0001). The 10398G SNP causes a nonconservative amino acid change from threonine to alanine within the NADH dehydrogenase 3 (ND3; 516002) of complex I. After stratification by sex, this decrease in risk appeared stronger in women than in men. In addition, the 9055A SNP of ATP6 (516060) demonstrated a protective effect for women. Van der Walt et al. (2003) concluded that ND3 may be an important factor in PD susceptibility among white individuals and could help explain the role of complex I in Parkinson disease expression. </p><p>By haplotype analysis of 455 patients with PD, 185 patients with Alzheimer disease (AD; 104300), and 447 controls, Pyle et al. (2005) found that the UKJT haplotype cluster (Torroni et al., 1996) was associated with a 22% reduction in risk for development of PD. There was no association between any haplotypes and AD, indicating that the association was specific for Parkinson disease. Reanalysis of the data reported by van der Walt et al. (2003) showed similar results for the pooled data of haplotypes U, K, J, and T. Pyle et al. (2005) noted that the 10398A-G polymorphism has been described on several other haplotypes (see Herrnstadt et al., 2002), indicating that the 10398A-G polymorphism does not 'define' haplotypes J and K, as asserted by van der Walt et al. (2003). </p><p>Horvath et al. (2007) reported a 66-year-old German man with parkinsonism due to an 8344A-G mutation in the MTTK gene (590060.0001). Symptoms included bradykinesia, resting tremor, and asymmetric rigidity. He also had proximal muscle weakness, hyporeflexia, decreased distal sensation, and bilateral hearing loss. Serum creatine kinase was elevated. He showed good response to levodopa. Skeletal muscle biopsy showed ragged-red fibers, fiber size variability, centrally placed nuclei, and atrophic and necrotic fibers. There was a mild decrease in some respiratory chain enzymes. The 8344A-G mutation was homoplasmic in muscle and 80% in leukocytes. A brother with progressive hearing loss since age 10 had 70% heteroplasmy in blood. </p><p>In a patient with early-onset Parkinson disease (PARK6; 605909) due to homozygous mutation in the PINK1 gene (608309.0002), Piccoli et al. (2008) identified homoplasmic mutations in the MTND5 (516005.0010) and MTND6 genes (516006.0008), respectively. The patient had onset at age 22 years. His mother, who was heterozygous for the PINK1 mutation, was also homoplasmic for both mitochondrial mutations and showed disease onset at age 53. The father was heterozygous for the PINK1 mutation only and was unaffected at age 79. Biochemical studies of the proband's fibroblasts showed mitochondrial dysfunction, with decreased amounts of cytochrome c oxidase, impaired complex I activity, and increased hydrogen peroxide generation. Piccoli et al. (2008) concluded that the presence of the mitochondrial mutations in combination with the PINK1 mutation may have accelerated the onset of the disease. </p>
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<strong>REFERENCES</strong>
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Di Monte, D. A.
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<strong>Mitochondrial DNA and Parkinson's disease.</strong>
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Neurology 41 (suppl. 2): 38-42, 1991.
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[PubMed: 1904141]
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[Full Text: https://doi.org/10.1212/wnl.41.5_suppl_2.38]
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Duvoisin, R. C.
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<strong>Genetics of Parkinson's disease.</strong>
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Adv. Neurol. 45: 307-312, 1986.
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Herrnstadt, C., Elson, J. L., Fahy, E., Preston, G., Turnbull, D. M., Anderson, C., Ghosh, S. S., Olefsky, J. M., Beal, M. F., Davis, R. E., Howell, N.
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<strong>Reduced-median-network analysis of complete mitochondrial DNA coding-region sequences for the major African, Asian, and European haplogroups.</strong>
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Am. J. Hum. Genet. 70: 1152-1171, 2002. Note: Erratum: Am. J. Hum. Genet. 71: 448 only, 2002.
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[PubMed: 11938495]
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[Full Text: https://doi.org/10.1086/339933]
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Horvath, R., Kley, R. A., Lochmuller, H., Vorgerd, M.
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<strong>Parkinson syndrome, neuropathy, and myopathy caused by the mutation A8344G (MERRF) in tRNA-lys.</strong>
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Neurology 68: 56-58, 2007.
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[PubMed: 17200493]
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[Full Text: https://doi.org/10.1212/01.wnl.0000250334.48038.7a]
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Ikebe, S., Tanaka, M., Ozawa, T.
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<strong>Point mutations of mitochondrial genome in Parkinson's disease.</strong>
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Molec. Brain Res. 28: 281-295, 1995.
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[PubMed: 7723627]
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[Full Text: https://doi.org/10.1016/0169-328x(94)00209-w]
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Marttila, R. J., Kaprio, J., Koskenvuo, M., Rinne, U. K.
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<strong>Parkinson's disease in a nationwide twin cohort.</strong>
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Neurology 38: 1217-1219, 1988.
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[PubMed: 3399070]
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[Full Text: https://doi.org/10.1212/wnl.38.8.1217]
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Mizuno, Y., Ohta, S., Tanaka, M., Takamiya, S., Suzuki, K., Sato, T., Oya, H., Ozawa, T., Kagawa, Y.
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<strong>Deficiencies in complex I subunits of the respiratory chain in Parkinson's disease.</strong>
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Biochem. Biophys. Res. Commun. 163: 1450-1455, 1989.
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[PubMed: 2551290]
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[Full Text: https://doi.org/10.1016/0006-291x(89)91141-8]
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Parker, W. D., Jr., Boyson, S. J., Parks, J. K.
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<strong>Abnormalities of the electron transport chain in idiopathic Parkinson's disease.</strong>
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Ann. Neurol. 26: 719-723, 1989.
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[PubMed: 2557792]
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[Full Text: https://doi.org/10.1002/ana.410260606]
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Parker, W. D., Jr., Swerdlow, R. H.
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<strong>Mitochondrial dysfunction in idiopathic Parkinson disease.</strong>
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Am. J. Hum. Genet. 62: 758-762, 1998.
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[PubMed: 9529370]
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[Full Text: https://doi.org/10.1086/301812]
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|
</li>
|
|
|
|
<li>
|
|
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|
|
Piccoli, C., Ripoli, M., Quarato, G., Scrima, R., D'Aprile, A., Boffoli, D., Margaglione, M., Criscuolo, C., De Michele, G., Sardanelli, A., Papa, S., Capitanio, N.
|
|
<strong>Coexistence of mutations in PINK1 and mitochondrial DNA in early onset parkinsonism. (Letter)</strong>
|
|
J. Med. Genet. 45: 596-602, 2008.
|
|
|
|
|
|
[PubMed: 18524835]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.2008.058628]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
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|
|
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|
|
Pyle, A., Foltynie, T., Tiangyou, W., Lambert, C., Keers, S. M., Allcock, L. M., Davison, J., Lewis, S. J., Perry, R. H., Barker, R., Burn, D. J., Chinnery, P. F.
|
|
<strong>Mitochondrial DNA haplogroup cluster UKJT reduces the risk of PD.</strong>
|
|
Ann. Neurol. 57: 564-567, 2005.
|
|
|
|
|
|
[PubMed: 15786469]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.20417]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shoffner, J. M., Watts, R. L., Juncos, J. L., Torroni, A., Wallace, D. C.
|
|
<strong>Mitochondrial oxidative phosphorylation defects in Parkinson's disease.</strong>
|
|
Ann. Neurol. 30: 332-339, 1991.
|
|
|
|
|
|
[PubMed: 1952821]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.410300304]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
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|
|
Swerdlow, R. H., Parks, J. K., Miller, S. W., Tuttle, J. B., Trimmer, P. A., Sheehan, J. P., Bennett, J. P., Jr., Davis, R. E., Parker, W. D., Jr.
|
|
<strong>Origin and functional consequences of the complex I defect in Parkinson's disease.</strong>
|
|
Ann. Neurol. 40: 663-671, 1996.
|
|
|
|
|
|
[PubMed: 8871587]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.410400417]
|
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|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
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|
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Torroni, A., Huoponen, K., Francalacci, P., Petrozzi, M., Morelli, L., Scozzari, R., Obinu, D., Savontaus, M.-L., Wallace, D. C.
|
|
<strong>Classification of European mtDNAs from an analysis of three European populations.</strong>
|
|
Genetics 144: 1835-1850, 1996.
|
|
|
|
|
|
[PubMed: 8978068]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/genetics/144.4.1835]
|
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|
|
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</p>
|
|
</li>
|
|
|
|
<li>
|
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<p class="mim-text-font">
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van der Walt, J. M., Nicodemus, K. K., Martin, E. R., Scott, W. K., Nance, M. A., Watts, R. L., Hubble, J. P., Haines, J. L., Koller, W. C., Lyons, K., Pahwa, R., Stern, M. B., and 15 others.
|
|
<strong>Mitochondrial polymorphisms significantly reduce the risk of Parkinson disease.</strong>
|
|
Am. J. Hum. Genet. 72: 804-811, 2003.
|
|
|
|
|
|
[PubMed: 12618962]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/373937]
|
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</p>
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</li>
|
|
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<li>
|
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<p class="mim-text-font">
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Vyas, I., Heikkila, R. E., Nicklas, W. J.
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<strong>Studies on the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: inhibition of NAD-linked substrate oxidation by its metabolite, 1-methyl-4-phenylpyridinium.</strong>
|
|
J. Neurochem. 46: 1501-1507, 1986.
|
|
|
|
|
|
[PubMed: 3485701]
|
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|
|
|
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[Full Text: https://doi.org/10.1111/j.1471-4159.1986.tb01768.x]
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</p>
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</li>
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<p class="mim-text-font">
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Zweig, R. M., Singh, A., Cardiollo, J. E., Langston, J. W.
|
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<strong>The familial occurrence of Parkinson's disease: lack of evidence for maternal inheritance.</strong>
|
|
Arch. Neurol. 49: 1205-1207, 1992. Note: Erratum: Arch. Neurol. 50: 153 only, 1993.
|
|
|
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|
|
[PubMed: 1288529]
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[Full Text: https://doi.org/10.1001/archneur.1992.00530350127029]
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