X-Linked Torsion Dystonia 3

An X-linked movement disorder that affects predominantly males of Filipino descent and is characterized by PARKINSONISM followed by DYSTONIA later in life. In the mildest cases, affected individuals have slowly progressive parkinsonism with little or no dystonia. More severe cases involve dystonia that rapidly becomes generalized. It is caused by an SVA (short interspersed nuclear element, variable number of tandem repeats, and Alu composite) RETROTRANSPOSON insertion in an INTRON of the TAF1 gene. OMIM: 314250

Also Known As:

Networked: 53 relevant articles (2 outcomes, 2 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Dystonia (Limb Dystonia)
2.	X-Linked Torsion Dystonia 3
3.	Parkinsonian Disorders (Parkinsonism)
4.	Neurodegenerative Diseases (Neurodegenerative Disease)
5.	Movement Disorders (Movement Disorder)

Experts

1.	Rosales, Raymond L: 15 articles (11/2022 - 10/2010)
2.	Diesta, Cid Czarina E: 10 articles (11/2022 - 01/2019)
3.	Klein, Christine: 10 articles (11/2022 - 09/2014)
4.	Brüggemann, Norbert: 9 articles (11/2022 - 09/2014)
5.	Westenberger, Ana: 9 articles (11/2022 - 09/2014)
6.	Sharma, Nutan: 8 articles (01/2022 - 04/2017)
7.	Schaake, Susen: 7 articles (11/2022 - 01/2019)
8.	Bragg, D Cristopher: 7 articles (01/2022 - 04/2017)
9.	Ozelius, Laurie J: 7 articles (01/2022 - 12/2017)
10.	Pozojevic, Jelena: 6 articles (11/2022 - 01/2019)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to X-Linked Torsion Dystonia 3:

1.	Retroelements (Retrotransposon)IBA 01/01/2023 - "X-linked Dystonia Parkinsonism (XDP) is associated with a SINE-VNTR- Alu (SVA) retrotransposon insertion in an intron of the TAF1 gene that alters gene transcription and splicing. " 11/01/2022 - "Elucidating Hexanucleotide Repeat Number and Methylation within the X-Linked Dystonia-Parkinsonism (XDP)-Related SVA Retrotransposon in TAF1 with Nanopore Sequencing." 02/17/2022 - "Transcriptional Alterations in X-Linked Dystonia-Parkinsonism Caused by the SVA Retrotransposon." 03/17/2020 - "Correction for Cristopher Bragg et al., Disease onset in X-linked dystonia-parkinsonism correlates with expansion of a hexameric repeat within an SVA retrotransposon in TAF1." 01/01/2018 - "(2) TAF1 reduction is a tractable molecular phenotype of X-linked dystonia-parkinsonism that can be driven by excision of the retrotransposon insertion. "
2.	Biomarkers (Surrogate Marker)IBA 01/01/2021 - "The objective of this study was to discover cell-based and biofluid-based biomarkers for X-linked dystonia-parkinsonism. " 10/01/2023 - "A Network Imaging Biomarker of X-Linked Dystonia-Parkinsonism." 01/01/2021 - "TAF1 Transcripts and Neurofilament Light Chain as Biomarkers for X-linked Dystonia-Parkinsonism."
3.	Proteins (Proteins, Gene)FDA Link 04/30/2010 - "Interestingly, our results also provide an unexpected link between DYT6 and DYT3 (X-linked dystonia-parkinsonism) dystonias because the gene encoding the THAP1/DYT6 protein partner OGT maps within the DYT3 critical region on Xq13.1." 01/01/2021 - "In this review, we provide an updated overview of the phenotypic and genetic spectrum of the most relevant X-linked parkinsonian syndromes, namely X-linked dystonia-parkinsonism (XDP, Lubag disease), fragile X-associated tremor/ataxia syndrome (FXTAS), beta-propeller protein-associated neurodegeneration (BPAN, NBIA/PARK-WDR45), Fabry disease, Waisman syndrome, methyl CpG-binding protein 2 (MeCP2) spectrum disorder, phosphoglycerate kinase-1 deficiency syndrome (PGK1) and X-linked parkinsonism and spasticity (XPDS). " 01/01/2020 - "Huntington's disease is caused by a polyglutamine-encoding CAG repeat expansion in the Huntingtin (HTT) gene leading to several toxic interactions of both the expanded CAG-containing mRNA and the polyglutamine-containing protein, while X-linked dystonia parkinsonism is caused by a retrotransposon insertion in the TAF1 gene, which decreases expression of this core scaffold of the basal transcription factor complex TFIID. "
4.	Dopamine Plasma Membrane Transport Proteins (Dopamine Transporter)IBA 01/01/2022 - "X-linked dystonia parkinsonism (XDP) or "Lubag" is a genetic dystonia syndrome observed among Filipinos that can present with levodopa-responsive parkinsonism and abnormal dopamine transporter (DAT) imaging. " 11/01/2010 - "We cover dopa-responsive dystonia, Wilson's disease, Parkin-, PINK1-, and DJ-1-associated parkinsonism (PARK2, 6, and 7), x-linked dystonia-parkinsonism/Lubag (DYT3), rapid-onset dystonia-parkinsonism (DYT12) and DYT16 dystonia, the syndromes of Neurodegeneration with Brain Iron Accumulation (NBIA) including pantothenate kinase (PANK2)- and PLA2G6 (PARK14)-associated neurodegeneration, neuroferritinopathy, Kufor-Rakeb disease (PARK9) and the recently described SENDA syndrome; FBXO7-associated neurodegeneration (PARK15), autosomal-recessive spastic paraplegia with a thin corpus callosum (SPG11), and dystonia parkinsonism due to mutations in the SLC6A3 gene encoding the dopamine transporter. "
5.	Type A Botulinum Toxins (Botox)FDA Link 01/01/2011 - "The broadening application of chemodenervation in X-linked dystonia-parkinsonism (Part I): muscle afferent block versus botulinum toxin-A in cervical and limb dystonias." 01/01/2011 - "The broadening application of chemodenervation in X-linked dystonia-parkinsonism (Part II): an open-label experience with botulinum toxin-A (Dysport®) injections for oromandibular, lingual, and truncal-axial dystonias." 01/01/2011 - "While the majority of chemodenervation clinics worldwide typically use botulinum toxins for the treatment of common conditions such as blepharopsams, cervical dystonia, limb dystonia, and spasticity, the unusually high concentration of X-linked dystonia-parkinsonism (XDP) has allowed us to collect and describe our experience in the use of botulinum toxin type A (BoNT-A) on rarer dystonic patterns. "
6.	Histones (Histone)IBA 01/01/2020 - "SVA insertion in X-linked Dystonia Parkinsonism alters histone H3 acetylation associated with TAF1 gene." 10/01/2020 - "Neuroinflammation and histone H3 citrullination are increased in X-linked Dystonia Parkinsonism post-mortem prefrontal cortex."
7.	DNA (Deoxyribonucleic Acid)IBA 09/01/2014 - "In a Filipino woman with suspected Parkinson disease, we confirmed the presence of all changes specific for X-linked dystonia-parkinsonism in genomic DNA. " 12/01/2020 - "DNA methylation at DSC12, DSC3, and DSC2 was quantified by bisulfite pyrosequencing in DNA from peripheral blood leukocytes, fibroblasts, induced pluripotent stem cell-derived cortical neurons and brain tissue from X-linked dystonia-parkinsonism patients and age- and sex-matched healthy Filipino controls in a prospective study. "
8.	Methyl-CpG-Binding Protein 2IBA 01/01/2021 - "In this review, we provide an updated overview of the phenotypic and genetic spectrum of the most relevant X-linked parkinsonian syndromes, namely X-linked dystonia-parkinsonism (XDP, Lubag disease), fragile X-associated tremor/ataxia syndrome (FXTAS), beta-propeller protein-associated neurodegeneration (BPAN, NBIA/PARK-WDR45), Fabry disease, Waisman syndrome, methyl CpG-binding protein 2 (MeCP2) spectrum disorder, phosphoglycerate kinase-1 deficiency syndrome (PGK1) and X-linked parkinsonism and spasticity (XPDS). "
9.	Transcription Factor TFIID (TFIID)IBA 01/01/2020 - "Huntington's disease is caused by a polyglutamine-encoding CAG repeat expansion in the Huntingtin (HTT) gene leading to several toxic interactions of both the expanded CAG-containing mRNA and the polyglutamine-containing protein, while X-linked dystonia parkinsonism is caused by a retrotransposon insertion in the TAF1 gene, which decreases expression of this core scaffold of the basal transcription factor complex TFIID. "
10.	TATA-Box Binding Protein (TATA-Binding Protein)IBA 12/19/2017 - "X-linked dystonia-parkinsonism (XDP) is a neurodegenerative disease associated with an antisense insertion of a SINE-VNTR-Alu (SVA)-type retrotransposon within an intron of TAF1 This unique insertion coincides with six additional noncoding sequence changes in TAF1, the gene that encodes TATA-binding protein-associated factor-1, which appear to be inherited together as an identical haplotype in all reported cases. "

Therapies and Procedures

1.	Deep Brain Stimulation 01/01/2019 - "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). " 01/01/2019 - "Long-term outcomes of pallidal deep brain stimulation in X-linked dystonia parkinsonism (XDP): Up to 84 months follow-up and review of literature." 08/01/2015 - "Biochemical mechanisms of pallidal deep brain stimulation in X-linked dystonia parkinsonism." 07/01/2014 - "Bilateral pallidal deep brain stimulation for X-linked dystonia-parkinsonism." 11/01/2013 - "Impulse control disorder in a patient with X-linked dystonia-parkinsonism after bilateral pallidal deep brain stimulation."
2.	Therapeutics 12/01/2020 - "We identified altered DNA methylation in X-linked dystonia-parkinsonism patients as a possible additional mechanism modulating TAF1 expression and putative novel targets for future therapies using DNA methylation-modifying agents. " 10/01/2010 - "X-linked dystonia parkinsonism: clinical phenotype, genetics and therapeutics." 01/01/2019 - "Anecdotal evidence suggests that deep brain stimulation (DBS) of the internal globus pallidus (GPi) is effective in ameliorating dystonia in X-linked dystonia parkinsonism (XDP), a disease that is usually refractive to medical therapy. "
3.	Nerve Block (Nerve Blocks) 01/01/2011 - "The broadening application of chemodenervation in X-linked dystonia-parkinsonism (Part I): muscle afferent block versus botulinum toxin-A in cervical and limb dystonias." 01/01/2011 - "The broadening application of chemodenervation in X-linked dystonia-parkinsonism (Part II): an open-label experience with botulinum toxin-A (Dysport®) injections for oromandibular, lingual, and truncal-axial dystonias." 01/01/2011 - "While the majority of chemodenervation clinics worldwide typically use botulinum toxins for the treatment of common conditions such as blepharopsams, cervical dystonia, limb dystonia, and spasticity, the unusually high concentration of X-linked dystonia-parkinsonism (XDP) has allowed us to collect and describe our experience in the use of botulinum toxin type A (BoNT-A) on rarer dystonic patterns. "
4.	Operative Surgical Procedures 09/15/2007 - "Intracranial surgical procedures for Lubag have been unsuccessful. "
5.	Injections 01/01/2011 - "The broadening application of chemodenervation in X-linked dystonia-parkinsonism (Part II): an open-label experience with botulinum toxin-A (Dysport®) injections for oromandibular, lingual, and truncal-axial dystonias."