Inherited Isolated Dystonia: Clinical Genetics and Gene Function

Dauer, William T.

doi:10.1007/s13311-014-0297-7

Cited by 21 publications

(22 citation statements)

References 114 publications

(155 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An in-frame deletion in the TOR1A gene that removes a single glutamic acid residue (DE-torsinA) causes the neurodevelopmental disorder DYT1 dystonia and results in redistribution of torsinA from the ER to the NE. [186][187][188][189] In both torsinA null and homozygous DE-torsinA knockin mice, the neuronal NE exhibited ultrastructural abnormalities, including INM-derived vesicles within the NE lumen 190 . Other data indicate that torsinA affects connections between the INM and ONM.…”

Section: Nuclear Morphology and Diseasementioning

confidence: 99%

Recent advances in understanding nuclear size and shape

Mukherjee

Chen

Levy

2016

Nucleus

View full text Add to dashboard Cite

Size and shape are important aspects of nuclear structure. While normal cells maintain nuclear size within a defined range, altered nuclear size and shape are associated with a variety of diseases. It is unknown if altered nuclear morphology contributes to pathology, and answering this question requires a better understanding of the mechanisms that control nuclear size and shape. In this review, we discuss recent advances in our understanding of the mechanisms that regulate nuclear morphology, focusing on nucleocytoplasmic transport, nuclear lamins, the endoplasmic reticulum, the cell cycle, and potential links between nuclear size and size regulation of other organelles. We then discuss the functional significance of nuclear morphology in the context of early embryonic development. Looking toward the future, we review new experimental approaches that promise to provide new insights into mechanisms of nuclear size control, in particular microfluidic-based technologies, and discuss how altered nuclear morphology might impact chromatin organization and physiology of diseased cells.

show abstract

Section: Nuclear Morphology and Diseasementioning

confidence: 99%

Recent advances in understanding nuclear size and shape

Mukherjee

Chen

Levy

2016

Nucleus

View full text Add to dashboard Cite

show abstract

“…Many inherited forms of dystonia arise during childhood or young adulthood, indicating that the pathogenic mutations disrupt CNS maturation. Several causative genes have been identified, but the link between their disruption and abnormalities of specific neurodevelopmental events is poorly understood (Dauer, 2014). Absence of this knowledge limits understanding of motor circuit development and the ability to advance models of disease pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

The DYT6 Dystonia Protein THAP1 Regulates Myelination within the Oligodendrocyte Lineage

et al. 2017

View full text Add to dashboard Cite

SUMMARY The childhood-onset motor disorder DYT6 dystonia is caused by loss-of-function mutations in the transcription factor THAP1, but the neurodevelopmental processes in which THAP1 participates are unknown. We find that THAP1 is essential for the timing of myelination initiation during CNS maturation. Conditional deletion of THAP1 in the CNS retards maturation of the oligodendrocyte (OL) lineage, delaying myelination and causing persistent motor deficits. The CNS myelination defect results from a cell autonomous requirement for THAP1 in the OL lineage, and is recapitulated in developmental assays performed on OL progenitor cells purified from Thap1 null mice. Loss of THAP1 function disrupts a core set of OL maturation genes and reduces the DNA occupancy of YY1, a transcription factor required for OL maturation. These studies establish a role for THAP1 transcriptional regulation at the inception of myelination, and implicate abnormal timing of myelination in the pathogenesis of childhood-onset dystonia.

show abstract

“…Distribution of ensuing motor symptoms may be focal, affecting one region only; segmental or multi-focal, affecting at least two regions; or generalised, affecting the trunk and at least two other regions (Albanese et al, 2013). Underlying aetiology may be inherited, acquired or idiopathic (Albanese et al, 2013); with at least three causative genes identified and validated (including DYT1, DYT6, DYT25; Dauer et al, 2014) In addition to these often disabling motor symptoms, several studies have reported abnormalities in cognition (Stamelou et al, 2012). However, there has been some inconsistency in the abnormalities reported, with several conflicting findings, and some studies reporting no impairment at all (Ostrem et al, 2011;Taylor et al, 1991;van Tricht et al, 2012).…”

Section: Introductionmentioning

confidence: 99%