{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T03:18:06Z","timestamp":1777346286812,"version":"3.51.4"},"reference-count":106,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T00:00:00Z","timestamp":1627430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["1ZIA-NS003154"],"award-info":[{"award-number":["1ZIA-NS003154"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["Z01-AG000949-02"],"award-info":[{"award-number":["Z01-AG000949-02"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In recent decades, genetic research has nominated promising pathways and biological insights contributing to the etiological landscape of parkinsonism-related dystonias and atypical parkinsonism-related syndromes. Several disease-causing mutations and genetic risk factors have been unraveled, providing a deeper molecular understanding of the complex genetic architecture underlying these conditions. These disorders are difficult to accurately diagnose and categorize, thus making genetics research challenging. On one hand, dystonia is an umbrella term linked to clinically heterogeneous forms of disease including dopa-responsive dystonia, myoclonus-dystonia, rapid-onset dystonia-parkinsonism and dystonia-parkinsonism, often viewed as a precursor to Parkinson\u2019s disease. On the other hand, atypical parkinsonism disorders, such as progressive supranuclear palsy, multiple system atrophy and corticobasal degeneration, are rare in nature and represent a wide range of diverse and overlapping phenotypic variabilities, with genetic research limited by sample size availability. The current review summarizes the plethora of available genetic information for these diseases, outlining limits and future directions.<\/jats:p>","DOI":"10.3390\/ijms22158100","type":"journal-article","created":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T11:12:52Z","timestamp":1627470772000},"page":"8100","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Genetic Landscape of Parkinsonism-Related Dystonias and Atypical Parkinsonism-Related Syndromes"],"prefix":"10.3390","volume":"22","author":[{"given":"Monica","family":"Diez-Fairen","sequence":"first","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pilar","family":"Alvarez Jerez","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joos","family":"Berghausen","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Bandres-Ciga","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Epidemiological Study of Dystonia in Europe (ESDE) (2000). Collaborative Group A Prevalence Study of Primary Dystonia in Eight European Countries. J. Neurol., 247, 787\u2013792.","DOI":"10.1007\/s004150070094"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1212\/01.WNL.0000026474.12594.0D","article-title":"The Prevalence of Primary Dystonia in the General Community","volume":"59","author":"Kiechl","year":"2002","journal-title":"Neurology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1007\/s00702-021-02314-2","article-title":"Dystonia Updates: Definition, Nomenclature, Clinical Classification, and Etiology","volume":"128","author":"Klein","year":"2021","journal-title":"J. Neural Transm."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1002\/mds.25475","article-title":"Phenomenology and Classification of Dystonia: A Consensus Update","volume":"28","author":"Albanese","year":"2013","journal-title":"Mov. Disord."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"104462","DOI":"10.1016\/j.nbd.2019.05.001","article-title":"Dystonia and Parkinson\u2019s Disease: What Is the Relationship?","volume":"132","author":"Shetty","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"117477","DOI":"10.1016\/j.jns.2021.117477","article-title":"Development of Parkinsonism after Long-Standing Cervical Dystonia-A Cohort","volume":"427","author":"Balint","year":"2021","journal-title":"J. Neurol. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1212\/WNL.37.6.1009","article-title":"Forms of Dystonia in Patients with Parkinson\u2019s Disease","volume":"37","author":"Kidron","year":"1987","journal-title":"Neurology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1001\/jamaneurol.2013.488","article-title":"Next-Generation Phenotyping Using the Parkin Example: Time to Catch up with Genetics","volume":"70","author":"Kasten","year":"2013","journal-title":"JAMA Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1136\/jnnp-2013-307294","article-title":"Isolated Limb Dystonia as Presenting Feature of Parkin Disease","volume":"85","author":"Elia","year":"2014","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/ana.410230112","article-title":"Dystonia in Parkinson\u2019s Disease: Clinical and Pharmacological Features","volume":"23","author":"Poewe","year":"1988","journal-title":"Ann. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1016\/S1474-4422(11)70232-0","article-title":"Primary Dystonia and Dystonia-plus Syndromes: Clinical Characteristics, Diagnosis, and Pathogenesis","volume":"10","author":"Phukan","year":"2011","journal-title":"Lancet Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"116992","DOI":"10.1016\/j.jns.2020.116992","article-title":"Orofacial Dystonia and Asssociated Bulbar Symptoms in Multiple System Atrophy: A Blinded Video Analysis","volume":"417","author":"Thongchuam","year":"2020","journal-title":"J. Neurol. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.pjnns.2017.11.004","article-title":"Comparison of Dystonia between Parkinson\u2019s Disease and Atypical Parkinsonism: The Clinical Usefulness of Dystonia Distribution and Characteristics in the Differential Diagnosis of Parkinsonism","volume":"52","author":"Yoon","year":"2018","journal-title":"Neurol. Neurochir. Polska"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1002\/mds.28485","article-title":"Genotype-Phenotype Relations for Isolated Dystonia Genes: MDSGene Systematic Review","volume":"36","author":"Lange","year":"2021","journal-title":"Mov. Disord."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1016\/S1474-4422(20)30312-4","article-title":"Monogenic Variants in Dystonia: An Exome-Wide Sequencing Study","volume":"19","author":"Zech","year":"2020","journal-title":"Lancet Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.parkreldis.2021.02.013","article-title":"Clinically Relevant Copy-Number Variants in Exome Sequencing Data of Patients with Dystonia","volume":"84","author":"Zech","year":"2021","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1002\/ana.410350405","article-title":"Dopa-Responsive Dystonia: Pathological and Biochemical Observations in a Case","volume":"35","author":"Rajput","year":"1994","journal-title":"Ann. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/ng1194-236","article-title":"Hereditary Progressive Dystonia with Marked Diurnal Fluctuation Caused by Mutations in the GTP Cyclohydrolase I Gene","volume":"8","author":"Ichinose","year":"1994","journal-title":"Nat. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2480","DOI":"10.1093\/brain\/awu179","article-title":"Parkinson\u2019s Disease in GTP Cyclohydrolase 1 Mutation Carriers","volume":"137","author":"Mencacci","year":"2014","journal-title":"Brain"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/S1474-4422(19)30320-5","article-title":"Identification of Novel Risk Loci, Causal Insights, and Heritable Risk for Parkinson\u2019s Disease: A Meta-Analysis of Genome-Wide Association Studies","volume":"18","author":"Nalls","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"231.e1","DOI":"10.1016\/j.neurobiolaging.2018.09.008","article-title":"Common and Rare GCH1 Variants Are Associated with Parkinson\u2019s Disease","volume":"73","author":"Rudakou","year":"2019","journal-title":"Neurobiol. Aging"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1001\/archneurol.2012.574","article-title":"Dopa-Responsive Dystonia Revisited: Diagnostic Delay, Residual Signs, and Nonmotor Signs","volume":"69","author":"Tadic","year":"2012","journal-title":"Arch. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1136\/jnnp.72.6.801","article-title":"Phenocopies in a Large GCH1 Mutation Positive Family with Dopa Responsive Dystonia: Confusing the Picture?","volume":"72","author":"Grimes","year":"2002","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1007\/s12031-019-01301-3","article-title":"A Compound Heterozygote for GCH1 Mutation Represents a Case of Atypical Dopa-Responsive Dystonia","volume":"68","author":"Giri","year":"2019","journal-title":"J. Mol. Neurosci."},{"key":"ref_25","first-page":"123","article-title":"A Point Mutation in the Tyrosine Hydroxylase Gene Associated with Segawa\u2019s Syndrome","volume":"95","author":"Dworniczak","year":"1995","journal-title":"Hum. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Cai, C., Shi, W., Zeng, Z., Zhang, M., Ling, C., Chen, L., Cai, C., Zhang, B., and Li, W.-D. (2013). GTP Cyclohydrolase I and Tyrosine Hydroxylase Gene Mutations in Familial and Sporadic Dopa-Responsive Dystonia Patients. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0065215"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"18539","DOI":"10.1074\/jbc.M601780200","article-title":"Mutations Phe785Leu and Thr618Met in Na+,K+-ATPase, Associated with Familial Rapid-Onset Dystonia Parkinsonism, Interfere with Na+ Interaction by Distinct Mechanisms","volume":"281","author":"Rodacker","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nn.2753","article-title":"The Neural Substrates of Rapid-Onset Dystonia-Parkinsonism","volume":"14","author":"Calderon","year":"2011","journal-title":"Nat. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S1474-4422(08)70022-X","article-title":"DYT16, a Novel Young-Onset Dystonia-Parkinsonism Disorder: Identification of a Segregating Mutation in the Stress-Response Protein PRKRA","volume":"7","author":"Camargos","year":"2008","journal-title":"Lancet Neurol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/S1474-4422(08)70075-9","article-title":"A Heterozygous Frameshift Mutation in PRKRA (DYT16) Associated with Generalised Dystonia in a German Patient","volume":"7","author":"Seibler","year":"2008","journal-title":"Lancet Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1002\/mds.25981","article-title":"DYT16 Revisited: Exome Sequencing Identifies PRKRA Mutations in a European Dystonia Family","volume":"29","author":"Zech","year":"2014","journal-title":"Mov. Disord."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1002\/mds.26583","article-title":"PRKRA Mutation Causing Early-Onset Generalized Dystonia-Parkinsonism (DYT16) in an Italian Family","volume":"31","author":"Quadri","year":"2016","journal-title":"Mov. Disord."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.parkreldis.2017.12.015","article-title":"The Prevalence of PRKRA Mutations in Idiopathic Dystonia","volume":"48","author":"Puga","year":"2018","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/S1474-4422(10)70269-6","article-title":"Clinical and Molecular Characterisation of Hereditary Dopamine Transporter Deficiency Syndrome: An Observational Cohort and Experimental Study","volume":"10","author":"Kurian","year":"2011","journal-title":"Lancet Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1086\/512129","article-title":"Reduced Neuron-Specific Expression of the TAF1 Gene Is Associated with X-Linked Dystonia-Parkinsonism","volume":"80","author":"Makino","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"E11020","DOI":"10.1073\/pnas.1712526114","article-title":"Disease Onset in X-Linked Dystonia-Parkinsonism Correlates with Expansion of a Hexameric Repeat within an SVA Retrotransposon in","volume":"114","author":"Bragg","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1002\/ana.25488","article-title":"A Hexanucleotide Repeat Modifies Expressivity of X-Linked Dystonia Parkinsonism","volume":"85","author":"Westenberger","year":"2019","journal-title":"Ann. Neurol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3216","DOI":"10.1038\/s41467-021-23491-4","article-title":"Identifying Genetic Modifiers of Age-Associated Penetrance in X-Linked Dystonia-Parkinsonism","volume":"12","author":"Laabs","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1002\/mds.23137","article-title":"The Diagnostic Challenge of Primary Dystonia: Evidence from Misdiagnosis","volume":"25","author":"Lalli","year":"2010","journal-title":"Mov. Disord."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1212\/CPJ.0b013e3182a78eb5","article-title":"Primary Dystonia Misinterpreted as Parkinson Disease: Video Case Presentation and Practical Clues","volume":"3","author":"Klepitskaya","year":"2013","journal-title":"Neurol. Clin. Pract."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1002\/mds.22375","article-title":"Responsiveness to Levodopa in Epsilon-Sarcoglycan Deletions","volume":"24","author":"Luciano","year":"2009","journal-title":"Mov. Disord."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s11910-018-0819-5","article-title":"Progressive Supranuclear Palsy: An Update","volume":"18","author":"Armstrong","year":"2018","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0165-0173(00)00019-9","article-title":"Tau Protein Isoforms, Phosphorylation and Role in Neurodegenerative Disorders","volume":"33","author":"Delacourte","year":"2000","journal-title":"Brain Res. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/0896-6273(89)90210-9","article-title":"Multiple Isoforms of Human Microtubule-Associated Protein Tau: Sequences and Localization in Neurofibrillary Tangles of Alzheimer\u2019s Disease","volume":"3","author":"Goedert","year":"1989","journal-title":"Neuron"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1002\/1531-8249(199909)46:3<325::AID-ANA8>3.0.CO;2-V","article-title":"Overexpression of Four-Repeat Tau mRNA Isoforms in Progressive Supranuclear Palsy but Not in Alzheimer\u2019s Disease","volume":"46","author":"Chambers","year":"1999","journal-title":"Ann. Neurol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3","DOI":"10.14802\/jmd.15060","article-title":"Clinical Approach to Progressive Supranuclear Palsy","volume":"9","author":"Ling","year":"2016","journal-title":"J. Mov. Disord."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e00557","DOI":"10.1002\/brb3.557","article-title":"Prevalence of Progressive Supranuclear Palsy in Yonago: Change throughout a Decade","volume":"6","author":"Takigawa","year":"2016","journal-title":"Brain Behav."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1038\/ng.859","article-title":"Identification of Common Variants Influencing Risk of the Tauopathy Progressive Supranuclear Palsy","volume":"43","author":"Melhem","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s13024-018-0270-8","article-title":"Joint Genome-Wide Association Study of Progressive Supranuclear Palsy Identifies Novel Susceptibility Loci and Genetic Correlation to Neurodegenerative Diseases","volume":"13","author":"Chen","year":"2018","journal-title":"Mol. Neurodegener."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1002\/mds.27702","article-title":"Genome-Wide Survey of Copy Number Variants Finds MAPT Duplications in Progressive Supranuclear Palsy","volume":"34","author":"Chen","year":"2019","journal-title":"Mov. Disord."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1159\/000319454","article-title":"Novel L284R MAPT Mutation in a Family with an Autosomal Dominant Progressive Supranuclear Palsy Syndrome","volume":"8","author":"Rohrer","year":"2011","journal-title":"Neurodegener. Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1001\/archneur.62.9.1444","article-title":"A New Mutation of the Tau Gene, G303V, in Early-Onset Familial Progressive Supranuclear Palsy","volume":"62","author":"Ros","year":"2005","journal-title":"Arch. Neurol."},{"key":"ref_53","first-page":"115","article-title":"Heritability in Frontotemporal Tauopathies","volume":"11","author":"Forrest","year":"2019","journal-title":"Alzheimers Dement."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1212\/WNL.0b013e3181a92bcc","article-title":"Familial Aggregation of Parkinsonism in Progressive Supranuclear Palsy","volume":"73","author":"Kaat","year":"2009","journal-title":"Neurology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1002\/mds.26987","article-title":"Clinical Diagnosis of Progressive Supranuclear Palsy: The Movement Disorder Society Criteria","volume":"32","author":"Respondek","year":"2017","journal-title":"Mov. Disord."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"93","DOI":"10.3233\/JPD-202302","article-title":"Genetics of Progressive Supranuclear Palsy: A Review","volume":"11","author":"Wen","year":"2021","journal-title":"J. Parkinsons Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1212\/WNL.53.4.864","article-title":"A Mutation in the Microtubule-Associated Protein Tau in Pallido-Nigro-Luysian Degeneration","volume":"53","author":"Yasuda","year":"1999","journal-title":"Neurology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1001\/archneur.60.10.1454","article-title":"A Case of Dementia Parkinsonism Resembling Progressive Supranuclear Palsy due to Mutation in the Tau Protein Gene","volume":"60","author":"Soliveri","year":"2003","journal-title":"Arch. Neurol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.parkreldis.2012.06.019","article-title":"Analyses of the MAPT, PGRN, and C9orf72 Mutations in Japanese Patients with FTLD, PSP, and CBS","volume":"19","author":"Ogaki","year":"2013","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"240.e13","DOI":"10.1016\/j.neurobiolaging.2019.02.016","article-title":"Tau Aggregation and Seeding Analyses of Two Novel MAPT Variants Found in Patients with Motor Neuron Disease and Progressive Parkinsonism","volume":"84","author":"Nakayama","year":"2019","journal-title":"Neurobiol. Aging"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.parkreldis.2014.10.028","article-title":"Three Sib-Pairs of Autopsy-Confirmed Progressive Supranuclear Palsy","volume":"21","author":"Fujioka","year":"2015","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1007\/s00702-009-0303-0","article-title":"The LRRK2 G2019S Mutation as the Cause of Parkinson\u2019s Disease in Ashkenazi Jews","volume":"116","author":"Thaler","year":"2009","journal-title":"J. Neural Transm."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S1474-4422(20)30394-X","article-title":"Genetic Determinants of Survival in Progressive Supranuclear Palsy: A Genome-Wide Association Study","volume":"20","author":"Jabbari","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1212\/01.wnl.0000240220.33950.0c","article-title":"Parkinsonism, Lrrk2 G2019S, and Tau Neuropathology","volume":"67","author":"Rajput","year":"2006","journal-title":"Neurology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1111\/j.1365-2990.2011.01216.x","article-title":"Atypical Tauopathy in a Patient with LRRK2-G2019S Mutation and Tremor-Dominant Parkinsonism","volume":"38","author":"Ruffmann","year":"2012","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1002\/mds.26815","article-title":"Study of LRRK2 Variation in Tauopathy: Progressive Supranuclear Palsy and Corticobasal Degeneration","volume":"32","author":"Heckman","year":"2017","journal-title":"Mov. Disord."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"214.e1","DOI":"10.1016\/j.neurobiolaging.2018.11.007","article-title":"Genetic Analysis of Neurodegenerative Diseases in a Pathology Cohort","volume":"76","author":"Blauwendraat","year":"2019","journal-title":"Neurobiol. Aging"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.neuron.2004.11.005","article-title":"Mutations in LRRK2 Cause Autosomal-Dominant Parkinsonism with Pleomorphic Pathology","volume":"44","author":"Zimprich","year":"2004","journal-title":"Neuron"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1212\/01.WNL.0000125015.06989.DB","article-title":"Autosomal Dominant Parkinsonism Associated with Variable Synuclein and Tau Pathology","volume":"62","author":"Wszolek","year":"2004","journal-title":"Neurology"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1212\/01.wnl.0000239829.33936.73","article-title":"LRRK2 Mutations on Crete: R1441H Associated with PD Evolving to PSP","volume":"67","author":"Spanaki","year":"2006","journal-title":"Neurology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1016\/j.parkreldis.2015.07.011","article-title":"Novel LRRK2 Mutations in Parkinsonism","volume":"21","author":"Trinh","year":"2015","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1001\/jamaneurol.2013.5100","article-title":"DCTN1 Mutation Analysis in Families with Progressive Supranuclear Palsy-like Phenotypes","volume":"71","author":"Caroppo","year":"2014","journal-title":"JAMA Neurol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.parkreldis.2016.04.025","article-title":"DCTN1 p.K56R in Progressive Supranuclear Palsy","volume":"28","author":"Gustavsson","year":"2016","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.parkreldis.2018.02.038","article-title":"DCTN1 F52L Mutation Case of Perry Syndrome with Progressive Supranuclear Palsy-like Tauopathy","volume":"51","author":"Honda","year":"2018","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1038\/s41598-018-19198-0","article-title":"Mutations in Bassoon in Individuals with Familial and Sporadic Progressive Supranuclear Palsy-like Syndrome","volume":"8","author":"Yabe","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1002\/mds.10264","article-title":"Steele-Richardson-Olszewski Syndrome in a Patient with a Single C212Y Mutation in the Parkin Protein","volume":"17","author":"Morales","year":"2002","journal-title":"Mov. Disord."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"399","DOI":"10.3233\/JAD-2002-4506","article-title":"Progressive Supranuclear Palsy and Tau Hyperphosphorylation in a Patient with a C212Y Parkin Mutation","volume":"4","author":"Gonzalo","year":"2002","journal-title":"J. Alzheimers Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1093\/brain\/aws357","article-title":"C9orf72 Repeat Expansions Are a Rare Genetic Cause of Parkinsonism","volume":"136","author":"Lesage","year":"2013","journal-title":"Brain"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"485","DOI":"10.3233\/JAD-121456","article-title":"C9ORF72 Repeat Expansions in the Frontotemporal Dementias Spectrum of Diseases: A Flow-Chart for Genetic Testing","volume":"34","author":"Camuzat","year":"2013","journal-title":"J. Alzheimers. Dis."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1007\/s00415-016-8021-7","article-title":"Atypical Parkinsonism in C9orf72 Expansions: A Case Report and Systematic Review of 45 Cases from the Literature","volume":"263","author":"Wilke","year":"2016","journal-title":"J. Neurol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1111\/ncn3.12041","article-title":"Frontotemporal Dementia and Progressive Supranuclear Palsy-like Syndrome with a novelTARDBPmutation","volume":"4","author":"Yabe","year":"2016","journal-title":"Neurol. Clin. Neurosci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2270","DOI":"10.1002\/mds.21146","article-title":"Mutations in NPC1 in Two Brazilian Patients with Niemann-Pick Disease Type C and Progressive Supranuclear Palsy-like Presentation","volume":"21","author":"Inaoka","year":"2006","journal-title":"Mov. Disord."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.3233\/JAD-160214","article-title":"Role of Niemann-Pick Type C Disease Mutations in Dementia","volume":"55","author":"Cupidi","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1002\/mds.23749","article-title":"Progressive Supranuclear Palsy-like Phenotype Caused by Progranulin p.Thr272fs Mutation","volume":"26","author":"Tremolizzo","year":"2011","journal-title":"Mov. Disord."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"244.e9","DOI":"10.1016\/j.neurobiolaging.2017.10.010","article-title":"Beyond ALS and FTD: The Phenotypic Spectrum of TBK1 Mutations Includes PSP-like and Cerebellar Phenotypes","volume":"62","author":"Wilke","year":"2018","journal-title":"Neurobiol. Aging"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1002\/ana.25308","article-title":"Variation at the TRIM11 Locus Modifies Progressive Supranuclear Palsy Phenotype","volume":"84","author":"Jabbari","year":"2018","journal-title":"Ann. Neurol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s40478-019-0769-4","article-title":"Cross-Examining Candidate Genes Implicated in Multiple System Atrophy","volume":"7","author":"Katzeff","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1007\/s00702-016-1545-2","article-title":"Multiple System Atrophy: Pathogenic Mechanisms and Biomarkers","volume":"123","author":"Jellinger","year":"2016","journal-title":"J. Neural Transm."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.parkreldis.2015.11.005","article-title":"Genome-Wide Estimate of the Heritability of Multiple System Atrophy","volume":"22","author":"Federoff","year":"2016","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1924.e5","DOI":"10.1016\/j.neurobiolaging.2011.04.001","article-title":"Genetic Players in Multiple System Atrophy: Unfolding the Nature of the Beast","volume":"32","author":"Stemberger","year":"2011","journal-title":"Neurobiol. Aging"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1002\/ana.21685","article-title":"SNCA Variants Are Associated with Increased Risk for Multiple System Atrophy","volume":"65","author":"Scholz","year":"2009","journal-title":"Ann. Neurol."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Al-Chalabi, A., D\u00fcrr, A., Wood, N.W., Parkinson, M.H., Camuzat, A., Hulot, J.-S., Morrison, K.E., Renton, A., Sussmuth, S.D., and Landwehrmeyer, B.G. (2009). Genetic Variants of the Alpha-Synuclein Gene SNCA Are Associated with Multiple System Atrophy. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007114"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Chen, Y., Wei, Q.-Q., Ou, R., Cao, B., Chen, X., Zhao, B., Guo, X., Yang, Y., Chen, K., and Wu, Y. (2015). Genetic Variants of SNCA Are Associated with Susceptibility to Parkinson\u2019s Disease but Not Amyotrophic Lateral Sclerosis or Multiple System Atrophy in a Chinese Population. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0133776"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"(2013). Multiple-System Atrophy Research Collaboration Mutations in COQ2 in Familial and Sporadic Multiple-System Atrophy. N. Engl. J. Med., 369, 233\u2013244.","DOI":"10.1056\/NEJMoa1212115"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/s10072-015-2414-8","article-title":"Association of the COQ2 V393A Variant with Risk of Multiple System Atrophy in East Asians: A Case-Control Study and Meta-Analysis of the Literature","volume":"37","author":"Zhao","year":"2016","journal-title":"Neurol. Sci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1212\/WNL.0000000000003221","article-title":"A Genome-Wide Association Study in Multiple System Atrophy","volume":"87","author":"Sailer","year":"2016","journal-title":"Neurology"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1002\/acn3.185","article-title":"Variants Associated with Gaucher Disease in Multiple System Atrophy","volume":"2","author":"Mitsui","year":"2015","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1002\/mdc3.12481","article-title":"Frequency of Variants in Autopsy-Proven Multiple System Atrophy","volume":"4","author":"Sklerov","year":"2017","journal-title":"Mov. Disord. Clin. Pract."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1212\/01.wnl.0000345356.40399.eb","article-title":"Glucocerebrosidase Mutations in 108 Neuropathologically Confirmed Cases of Multiple System Atrophy","volume":"72","author":"Segarane","year":"2009","journal-title":"Neurology"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1590\/1980-57642020dn14-030006","article-title":"Pharmacological Interventions in Corticobasal Degeneration: A Review","volume":"14","author":"Caixeta","year":"2020","journal-title":"Dement. Neuropsychol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/nrneurol.2011.43","article-title":"Corticobasal Degeneration: A Pathologically Distinct 4R Tauopathy","volume":"7","author":"Kouri","year":"2011","journal-title":"Nat. Rev. Neurol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/bs.irn.2019.10.014","article-title":"Corticobasal Degeneration","volume":"149","author":"Saranza","year":"2019","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1212\/WNL.0b013e31827f0fd1","article-title":"Criteria for the Diagnosis of Corticobasal Degeneration","volume":"80","author":"Armstrong","year":"2013","journal-title":"Neurology"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"7247","DOI":"10.1038\/ncomms8247","article-title":"Genome-Wide Association Study of Corticobasal Degeneration Identifies Risk Variants Shared with Progressive Supranuclear Palsy","volume":"6","author":"Kouri","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1007\/s00401-017-1693-y","article-title":"Shared Genetic Risk between Corticobasal Degeneration, Progressive Supranuclear Palsy, and Frontotemporal Dementia","volume":"133","author":"Yokoyama","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1007\/s00401-019-02045-5","article-title":"C9orf72 Intermediate Repeats Are Associated with Corticobasal Degeneration, Increased C9orf72 Expression and Disruption of Autophagy","volume":"138","author":"Cali","year":"2019","journal-title":"Acta Neuropathol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/15\/8100\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:36:24Z","timestamp":1760164584000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/15\/8100"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,28]]},"references-count":106,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["ijms22158100"],"URL":"https:\/\/doi.org\/10.3390\/ijms22158100","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,28]]}}}