A Woman With a Novel Mutation ofTHAP1With a Prominent Response to Deep Brain Stimulation of the Globus Pallidus Internus

Park, Jung E.; Vanegas‐Arroyave, Nora; Hallett, Mark; Lungu, Codrin

doi:10.1001/jamaneurol.2015.1954

Cited by 4 publications

(3 citation statements)

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“…One patient from India with a novel THAP1 frameshift deletion mutation (c.208-209delAA; p.K70VfsX15) also showed a positive response to GPi DBS even after ten years, with particular response of lower limb and truncal dystonia [ 8 ]. A recent report of a patient with a novel base pair deletion mutation in exon 3 of the THAP1 gene showed a good response to GPi DBS; however, this was during only two months of follow up, unlike our patient who had a sustained DBS response even after over eight years post-implantation [ 9 ].…”

Section: Discussioncontrasting

confidence: 65%

Generalized Dystonia Due to a Pathogenic THAP1 Variant Showing Sustained Response to Globus Pallidus Deep Brain Stimulation

Bhattacharjee,

Silverdale,

Bonello

et al. 2023

TOHM

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A 21-year-old woman of south Asian origin presented with cervical dystonia which had progressed over the previous three years. Her symptoms started as writer’s cramp since the age of seven years. She did not respond to medications and needed botulinum toxin injection for generalised dystonia. Subsequent whole genome sequencing revealed a likely pathogenic c.98G>A p.(Cys33Tyr) heterozygous variant in the THAP1 gene. She underwent bilateral posteroventral globus pallidus interna (GPi) deep brain stimulation (Medtronic Activa PC) implantation at the age of thirty-one years. She responded well to the deep brain stimulation even after more than 8 years post-surgery though she needs botulinum toxin injection for her cervical dystonia.

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Section: Discussioncontrasting

confidence: 65%

Generalized Dystonia Due to a Pathogenic THAP1 Variant Showing Sustained Response to Globus Pallidus Deep Brain Stimulation

Bhattacharjee,

Silverdale,

Bonello

et al. 2023

TOHM

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“…A case-control study found the c.208 A>G (p.K70E) mutation in one of 70 MS patients, and this mutation was not seen in Greek controls and has not been reported in any control series published or available on-line (52). Whole-exome sequencing revealed a frameshift mutation in one MS patient, confirmed as a novel 2-base pair deletion mutation in exon 3 of the THAP1 gene (heterozygous exon 3 c.377_378delCT, p.Pro126Args * 2) via full sequencing analysis of DYT6 (65). In silico and minigene analyses indicated that c.71+9C>A alters THAP1 splicing and this variant is a risk factor (67).…”

Section: Geneticsmentioning

confidence: 99%

Blepharospasm, Oromandibular Dystonia, and Meige Syndrome: Clinical and Genetic Update

Liang-jun

et al. 2021

Front. Neurol.

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Meige syndrome (MS) is cranial dystonia characterized by the combination of upper and lower cranial involvement and including binocular eyelid spasms (blepharospasm; BSP) and involuntary movements of the jaw muscles (oromandibular dystonia; OMD). The etiology and pathogenesis of this disorder of the extrapyramidal system are not well-understood. Neurologic and ophthalmic examinations often reveal no abnormalities, making diagnosis difficult and often resulting in misdiagnosis. A small proportion of patients have a family history of the disease, but to date no causative genes have been identified to date and no cure is available, although botulinum toxin A therapy effectively mitigates the symptoms and deep brain stimulation is gaining increasing attention as a viable alternative treatment option. Here we review the history and progress of research on MS, BSP, and OMD, as well as the etiology, pathology, diagnosis, and treatment.

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“…It is well known that DBS effect is highly dependent on genotype, and particular mutations and variants within the same gene can result in divergent effects. 57 Better imaging technology would allow precisely defining the target and determining the location of each implanted lead, assessing the relative role of new DBS technology (directional leads, multiple current sources, sensing, and novel programming algorithms), and understanding the pathophysiologic basis underlying the development of dystonia, the network changes that occur, and the mechanism(s) underlying the improvement after DBS.…”

Section: Research Priorities Regarding Research Resources For Dystoniamentioning

confidence: 99%

Defining research priorities in dystonia

et al. 2020

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ObjectiveDystonia is a complex movement disorder. Research progress has been difficult, particularly in developing widely effective therapies. This is a review of the current state of knowledge, research gaps, and proposed research priorities.MethodsThe NIH convened leaders in the field for a 2-day workshop. The participants addressed the natural history of the disease, the underlying etiology, the pathophysiology, relevant research technologies, research resources, and therapeutic approaches and attempted to prioritize dystonia research recommendations.ResultsThe heterogeneity of dystonia poses challenges to research and therapy development. Much can be learned from specific genetic subtypes, and the disorder can be conceptualized along clinical, etiology, and pathophysiology axes. Advances in research technology and pooled resources can accelerate progress. Although etiologically based therapies would be optimal, a focus on circuit abnormalities can provide a convergent common target for symptomatic therapies across dystonia subtypes. The discussions have been integrated into a comprehensive review of all aspects of dystonia.ConclusionOverall research priorities include the generation and integration of high-quality phenotypic and genotypic data, reproducing key features in cellular and animal models, both of basic cellular mechanisms and phenotypes, leveraging new research technologies, and targeting circuit-level dysfunction with therapeutic interventions. Collaboration is necessary both for collection of large data sets and integration of different research methods.

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A Woman With a Novel Mutation ofTHAP1With a Prominent Response to Deep Brain Stimulation of the Globus Pallidus Internus

Cited by 4 publications

References 4 publications

Generalized Dystonia Due to a Pathogenic <em>THAP1</em> Variant Showing Sustained Response to Globus Pallidus Deep Brain Stimulation

Generalized Dystonia Due to a Pathogenic <em>THAP1</em> Variant Showing Sustained Response to Globus Pallidus Deep Brain Stimulation

Blepharospasm, Oromandibular Dystonia, and Meige Syndrome: Clinical and Genetic Update

Defining research priorities in dystonia

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A Woman With a Novel Mutation ofTHAP1With a Prominent Response to Deep Brain Stimulation of the Globus Pallidus Internus

Cited by 4 publications

References 4 publications

Generalized Dystonia Due to a Pathogenic <em>THAP1</em>&nbsp;Variant Showing Sustained Response to Globus Pallidus Deep Brain Stimulation

Generalized Dystonia Due to a Pathogenic <em>THAP1</em>&nbsp;Variant Showing Sustained Response to Globus Pallidus Deep Brain Stimulation

Blepharospasm, Oromandibular Dystonia, and Meige Syndrome: Clinical and Genetic Update

Defining research priorities in dystonia

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Product

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Generalized Dystonia Due to a Pathogenic <em>THAP1</em> Variant Showing Sustained Response to Globus Pallidus Deep Brain Stimulation

Generalized Dystonia Due to a Pathogenic <em>THAP1</em> Variant Showing Sustained Response to Globus Pallidus Deep Brain Stimulation