X-Linked Dystonia-Parkinsonism: Recent Advances

Overview

Journal Curr Opin Neurol

Specialty Neurology

Date 2019 May 23

PMID 31116117

Citations 12

Authors

D Cristopher Bragg

Nutan Sharma

Laurie J Ozelius

Affiliations

Soon will be listed here.

Abstract

Purpose Of Review: Our understanding of X-Linked Dystonia-Parkinsonism (XDP) has advanced considerably in recent years because of a wealth of new data describing its genetic basis, cellular phenotypes, neuroimaging features, and response to deep brain stimulation (DBS). This review provides a concise summary of these studies.

Recent Findings: XDP is associated with a SINE-VNTR-Alu (SVA)-type retrotransposon insertion within the TAF1 gene. This element includes a hexameric DNA repeat expansion, (CCCTCT)n, the length of which varies among patients and is inversely correlated to age of disease onset. In cell models, the SVA alters TAF1 splicing and reduces levels of full-length transcript. Neuroimaging data have confirmed previous neuropathology studies that XDP involves a progressive striatal atrophy, while further detecting functional alterations in additional brain regions. In patients exhibiting features of both dystonia and parkinsonism, pallidal DBS has resulted in rapid improvement of hyperkinetic movements, but effects on hypokinetic features have been inconsistent.

Summary: The discovery that XDP is linked to a polymorphic hexameric sequence suggests that it could share mechanisms with other DNA repeat disorders, whereas the transcriptional defect in cell models raises the possibility that strategies to correct TAF1 splicing could provide therapeutic benefit.

Citing Articles

Targeting Myeloperoxidase to Reduce Neuroinflammation in X-Linked Dystonia Parkinsonism.

Petrozziello T, Jalali Motlagh N, Monsanto R, Lei D, Murcar M, Penney E CNS Neurosci Ther. 2024; 30(11):e70109.

PMID: 39500625 PMC: 11537767. DOI: 10.1111/cns.70109.

Mini-heterochromatin domains constrain the cis-regulatory impact of SVA transposons in human brain development and disease.

Horvath V, Garza R, Jonsson M, Johansson P, Adami A, Christoforidou G Nat Struct Mol Biol. 2024; 31(10):1543-1556.

PMID: 38834915 PMC: 11479940. DOI: 10.1038/s41594-024-01320-8.

Taf1 knockout is lethal in embryonic male mice and heterozygous females show weight and movement disorders.

Crombie E, Korecki A, Cleverley K, Adair B, Cunningham T, Lee W Dis Model Mech. 2024; 17(7).

PMID: 38804708 PMC: 11261634. DOI: 10.1242/dmm.050741.

Nine Hereditary Movement Disorders First Described in Asia: Their History and Evolution.

Jagota P, Ugawa Y, Aldaajani Z, Mohamed Ibrahim N, Ishiura H, Nomura Y J Mov Disord. 2023; 16(3):231-247.

PMID: 37309109 PMC: 10548072. DOI: 10.14802/jmd.23065.

Variation in TAF1 expression in female carrier induced pluripotent stem cells and human brain ontogeny has implications for adult neostriatum vulnerability in X-linked Dystonia Parkinsonism.

DIgnazio L, Jacomini R, Qamar B, Benjamin K, Arora R, Sawada T eNeuro. 2022; .

PMID: 35868859 PMC: 9428949. DOI: 10.1523/ENEURO.0129-22.2022.

References

Bruggemann N, Heldmann M, Klein C, Domingo A, Rasche D, Tronnier V . Neuroanatomical changes extend beyond striatal atrophy in X-linked dystonia parkinsonism. Parkinsonism Relat Disord. 2016; 31:91-97. DOI: 10.1016/j.parkreldis.2016.07.012. View

Stewart C, Kural D, Stromberg M, Walker J, Konkel M, Stutz A . A comprehensive map of mobile element insertion polymorphisms in humans. PLoS Genet. 2011; 7(8):e1002236. PMC: 3158055. DOI: 10.1371/journal.pgen.1002236. View

Domingo A, Westenberger A, Lee L, Braenne I, Liu T, Vater I . New insights into the genetics of X-linked dystonia-parkinsonism (XDP, DYT3). Eur J Hum Genet. 2015; 23(10):1334-40. PMC: 4592086. DOI: 10.1038/ejhg.2014.292. View

Lee L, PASCASIO F, Fuentes F, Viterbo G . Torsion dystonia in Panay, Philippines. Adv Neurol. 1976; 14:137-51. View

Makino S, Kaji R, Ando S, Tomizawa M, Yasuno K, Goto S . Reduced neuron-specific expression of the TAF1 gene is associated with X-linked dystonia-parkinsonism. Am J Hum Genet. 2007; 80(3):393-406. PMC: 1821114. DOI: 10.1086/512129. View

Okamoto N, Arai H, Onishi T, Mizuguchi T, Matsumoto N . Intellectual disability and dysmorphic features in male siblings arising from a novel TAF1 mutation. Congenit Anom (Kyoto). 2019; 60(1):40-41. DOI: 10.1111/cga.12330. View

Nolte D, Niemann S, Muller U . Specific sequence changes in multiple transcript system DYT3 are associated with X-linked dystonia parkinsonism. Proc Natl Acad Sci U S A. 2003; 100(18):10347-52. PMC: 193564. DOI: 10.1073/pnas.1831949100. View

Morigaki R, Nakataki M, Kawarai T, Lee L, Teleg R, Tabuena M . Depression in X-linked dystonia-parkinsonism: a case-control study. Parkinsonism Relat Disord. 2013; 19(9):844-6. DOI: 10.1016/j.parkreldis.2013.04.027. View

Patel A, Sarwar A, Jankovic J, Viswanathan A . Bilateral pallidal deep brain stimulation for X-linked dystonia-parkinsonism. World Neurosurg. 2013; 82(1-2):241.e1-4. DOI: 10.1016/j.wneu.2013.09.039. View

10.

Pasco P, Jamora R, Rosales R, Diesta C, Ng A, Teleg R . Validation of the XDP-MDSP rating scale for the evaluation of patients with X-linked dystonia-parkinsonism. NPJ Parkinsons Dis. 2017; 3:24. PMC: 5526880. DOI: 10.1038/s41531-017-0026-0. View

11.

Fischer V, Schumacher K, Tora L, Devys D . Global role for coactivator complexes in RNA polymerase II transcription. Transcription. 2018; 10(1):29-36. PMC: 6351120. DOI: 10.1080/21541264.2018.1521214. View

12.

Lee L, Kupke K, Muller U . The phenotype of the X-linked dystonia-parkinsonism syndrome. An assessment of 42 cases in the Philippines. Medicine (Baltimore). 1991; 70(3):179-87. DOI: 10.1097/00005792-199105000-00002. View

13.

Hancks D, Kazazian Jr H . Roles for retrotransposon insertions in human disease. Mob DNA. 2016; 7:9. PMC: 4859970. DOI: 10.1186/s13100-016-0065-9. View

14.

Evidente V, Esteban R, Hernandez J, Natividad F, Advincula J, Gwinn-Hardy K . Smell testing is abnormal in 'lubag' or X-linked dystonia-parkinsonism: a pilot study. Parkinsonism Relat Disord. 2004; 10(7):407-10. DOI: 10.1016/j.parkreldis.2004.04.011. View

15.

Jamora R, Diesta C, Pasco P, Lee L . Oral pharmacological treatment of X-linked dystonia parkinsonism: successes and failures. Int J Neurosci. 2011; 121 Suppl 1:18-21. DOI: 10.3109/00207454.2010.544433. View

16.

Goto S, Kawarai T, Morigaki R, Okita S, Koizumi H, Nagahiro S . Defects in the striatal neuropeptide Y system in X-linked dystonia-parkinsonism. Brain. 2013; 136(Pt 5):1555-67. DOI: 10.1093/brain/awt084. View

17.

Kilbane C, Witt J, Galifianakis N, Glass G, Volz M, Heath S . Long-Term Outcomes of Bilateral Pallidal Deep Brain Stimulation for X-Linked Dystonia and Parkinsonism. Stereotact Funct Neurosurg. 2018; 96(5):320-326. DOI: 10.1159/000492823. View

18.

Aneichyk T, Hendriks W, Yadav R, Shin D, Gao D, Vaine C . Dissecting the Causal Mechanism of X-Linked Dystonia-Parkinsonism by Integrating Genome and Transcriptome Assembly. Cell. 2018; 172(5):897-909.e21. PMC: 5831509. DOI: 10.1016/j.cell.2018.02.011. View

19.

Beste C, Muckschel M, Rosales R, Domingo A, Lee L, Ng A . Striosomal dysfunction affects behavioral adaptation but not impulsivity-Evidence from X-linked dystonia-parkinsonism. Mov Disord. 2017; 32(4):576-584. DOI: 10.1002/mds.26895. View

20.

WATERS C, Faust P, Powers J, Vinters H, Moskowitz C, Nygaard T . Neuropathology of lubag (x-linked dystonia parkinsonism). Mov Disord. 1993; 8(3):387-90. DOI: 10.1002/mds.870080328. View