Clinical and Neuroradiological Features of Patients With Spinocerebellar Ataxias From Korean Kindreds

Bang, Oh Young; Huh, Kyu Ha; Lee, Phil Hyu; Kim, Hyon J.

doi:10.1001/archneur.60.11.1566

Cited by 30 publications

(17 citation statements)

References 35 publications

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“…Our gene analysis data showed that the number of CAG repeats in SCA2 coding region of the proband was 44 times, her mother was 36 times, and her brother was 38 times. All CAG repeats were found within the abnormal range, and this observation was consistent with the findings of a previous study [14]. The above-referred changes were found to have a negative correlation with age at which the disease onset occurred.…”

Section: Discussionsupporting

confidence: 92%

Clinical Manifestation, Imaging, and Genotype Analysis of Two Pedigrees with Spinocerebellar Ataxia

Liu

et al. 2011

Cell Biochem Biophys

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The objective of this study was to analyze the clinical manifestation, imaging characteristics, genotype, and the relationship between the three aforementioned parameters in two pedigrees suffering from spinocerebellar ataxia. To evaluate the clinical manifestation of the two pedigrees and to compare the characteristics, we performed the MRI analysis of some patients from both pedigrees, while 2 ml of the peripheral blood sample was collected for gene analysis. The gene analysis data showed that pedigree 1 was certified spinocerebellar ataxia type-2 (SCA2); the CAG repeats in the proband, proband's mother, and proband's brother were 44, 36, and 38, respectively. The MRI revealed brainstem cerebellar atrophy and "cross sign" and "ordinate sign" of pons. Pedigree 2 was certified SCA1; the CAG repeats of the proband, proband's aunt, and proband's asymptomatic cousin were 60, 51, and 52, respectively. The MRI revealed cerebellar atrophy in these individuals. We, therefore, concluded that it was difficult to diagnose the SCA subset solely through the clinical manifestation. The imaging characteristics analysis and final diagnosis depended basically on gene analysis data.

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Section: Discussionsupporting

confidence: 92%

Clinical Manifestation, Imaging, and Genotype Analysis of Two Pedigrees with Spinocerebellar Ataxia

Liu

et al. 2011

Cell Biochem Biophys

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“…Given the diversity of dystonias, it would be surprising if both cases are not rampant. Nonetheless there are clear examples of dystonia in patients that appear to be causally related to cerebellar dysfunction, particularly when dystonia manifests as a symptom in cerebellar-centric disorders such as spinocerebellar or episodic ataxias (Bang et al, 2003; Kawarai et al, 2016; Mariotti et al, 2007; Muglan et al, 2016; Nakagaki et al, 2002; Sethi and Jankovic, 2002). In some cases, lesioning or stimulation of the cerebellum has been documented to improve the symptoms, corroborating the notion that in some patients, dystonia can arise from cerebellar dysfunction (Koch et al, 2014; Panov et al, 2013; Teixeira et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

A role for cerebellum in the hereditary dystonia DYT1

Fremont

Tewari

Angueyra

et al. 2017

eLife

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DYT1 is a debilitating movement disorder caused by loss-of-function mutations in torsinA. How these mutations cause dystonia remains unknown. Mouse models which have embryonically targeted torsinA have failed to recapitulate the dystonia seen in patients, possibly due to differential developmental compensation between rodents and humans. To address this issue, torsinA was acutely knocked down in select brain regions of adult mice using shRNAs. TorsinA knockdown in the cerebellum, but not in the basal ganglia, was sufficient to induce dystonia. In agreement with a potential developmental compensation for loss of torsinA in rodents, torsinA knockdown in the immature cerebellum failed to produce dystonia. Abnormal motor symptoms in knockdown animals were associated with irregular cerebellar output caused by changes in the intrinsic activity of both Purkinje cells and neurons of the deep cerebellar nuclei. These data identify the cerebellum as the main site of dysfunction in DYT1, and offer new therapeutic targets.DOI: http://dx.doi.org/10.7554/eLife.22775.001

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“…Magnetic Resonance Imaging (MRI) of SCA7 patients typically reveals marked atrophy of the cerebellum and pons (Figure 1b), while a subset of patients may also demonstrate high T2 signal intensity in transverse pontine fibers (16). MRIbased volumetric analysis demonstrated that SCA7 patients have significantly more pontine atrophy than patients with other SCAs.…”

Section: Genetic Features Of Sca7mentioning

confidence: 99%

Molecular pathogenesis and cellular pathology of spinocerebellar ataxia type 7 neurodegeneration

2008

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Spinocerebellar ataxia type 7 (SCA7) is unique among CAG/polyglutamine (polyQ) repeat diseases due to dramatic intergenerational instability in repeat length and an associated cone-rod dystrophy retinal degeneration phenotype. SCA7 is caused by a polyQ expansion in the protein ataxin-7. Like other neurodegenerative diseases caused by polyQ expansion mutations, the spectrum of clinical severity and disease progression worsens with increasing polyQ length. Several potential mechanisms for the molecular pathogenesis of polyQ-expanded ataxin-7 have been suggested. These include, but are not limited to, alteration of endogenous ataxin-7 function, abnormal processing and stability of polyQ ataxin-7, and alteration of transcriptional regulation via interaction of polyQ-expanded ataxin-7 with other transcriptional regulators. Ataxin-7's normal function as a transcription factor may contribute to the selective vulnerability of specific cellular populations in SCA7, and the resolution of the mechanistic basis of this pathogenic cascade is a major focus of SCA7 disease research. PolyQ-expanded ataxin-7 can cause non-cell autonomous neurodegeneration in cerebellar Purkinje cells. Advances in understanding SCA7's molecular basis have led to important insights into cell-type specific neurodegeneration. We expect that further study of ataxin-7 normal function, insights into the molecular basis of SCA7 neurodegeneration, and the development of therapeutic interventions for SCA7 will greatly influence related endeavors directed at other CAG/polyQ repeat diseases.

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Clinical and Neuroradiological Features of Patients With Spinocerebellar Ataxias From Korean Kindreds

Abstract: The clinical and neuroradiological characteristics of Korean patients with SCAs might be helpful in detecting underlying gene mutations.

Cited by 30 publications

References 35 publications

Clinical Manifestation, Imaging, and Genotype Analysis of Two Pedigrees with Spinocerebellar Ataxia

Clinical Manifestation, Imaging, and Genotype Analysis of Two Pedigrees with Spinocerebellar Ataxia

A role for cerebellum in the hereditary dystonia DYT1

Molecular pathogenesis and cellular pathology of spinocerebellar ataxia type 7 neurodegeneration

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