Spinocerebellar ataxia types 1, 2, 3, and 6

Schmitz‐Hübsch, Tanja; Coudert, Mathieu; Bauer, Péter; Giunti, Paola; Globas, Christoph; Balikó, László; Filla, Alessandro; Mariotti, Caterina; Rakowicz, Maria; Charles, Perrine; Ribaı̈, Pascale; Szymanski, Sandra; Infante, Jon; Warrenburg, Bart P. van de; Dürr, Alexandra; Timmann, Dagmar; Boesch, Sylvia; Fancellu, Roberto; Rola, Rafał; Depondt, Chantal; Schöls, Lüdger; Zdienicka, E; Kang, Jun-Suk; Döhlinger, Susanne; Kremer, Berry; Stephenson, Dennis A.; Melegh, Béla; Pandolfo, Massimo; Donato, Stefano Di; Montcel, Sophie Tezenas du; Klockgether, Thomas

doi:10.1212/01.wnl.0000325057.33666.72

Cited by 243 publications

(232 citation statements)

References 21 publications

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“…Because approximately 25% of all patients with SCA6 are affected by such extracerebellar oculomotor signs, ICARS may be superior to SARA when correlating extracerebellar MR imaging findings with clinical dysfunction. 26 Closer inspection of the correlations between ICARS subscore groups and volumes of infratentorial structures revealed a significant correlation in SCA3 between cerebellar volume and oculomotor function, while in SCA6, brain stem volume correlated significantly to kinetic functions and oculomotor functions.…”

Section: Discussionmentioning

confidence: 93%

Quantitative Assessment of Brain Stem and Cerebellar Atrophy in Spinocerebellar Ataxia Types 3 and 6: Impact on Clinical Status

Eichler¹,

Bellenberg²,

Hahn³

et al. 2011

AJNR Am J Neuroradiol

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Section: Discussionmentioning

confidence: 93%

Quantitative Assessment of Brain Stem and Cerebellar Atrophy in Spinocerebellar Ataxia Types 3 and 6: Impact on Clinical Status

Eichler¹,

Bellenberg²,

Hahn³

et al. 2011

AJNR Am J Neuroradiol

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“…A comprehensive study on the frequency of nonataxic symptoms was conducted in 2008 by Klockgether and colleagues who found that SCA6 had a lower frequency in all but one (rigidity) of the 16 nonataxic symptoms when compared to SCA1, 2 and 3. These features included a number of very common symptoms such as; brainstem oculomotor signs, hyperreflexia, extensor planter and muscular atrophy [159]. It was also found that disease severity is largely age-dependent rather than linked to expansion size.…”

Section: Sca6 Clinical Featuresmentioning

confidence: 96%

“…The CAG expansion is seen in the α 1A voltage-dependant calcium channel gene (CACNA1), localised to 19p13 [39]. The expansion in CACNA1 is located in the last exon of the gene (exon 47) and is relatively small compared to those in other SCA diseases, with a healthy range of 4-18 repeats and a disease range of 21-30 repeats, with most cases being reported as 22-23 repeats (Table 2) [159,160].…”

Section: Molecular Geneticsmentioning

confidence: 99%

Polyglutamine ataxias: From Clinical and Molecular Features to Current Therapeutic Strategies

McIntosh¹,

Htut²,

Fletcher³

et al. 2017

J Genet Syndr Gene Ther

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Spinocerebellar ataxias are a large group of heterogeneous diseases that all involve selective neuronal degeneration and accompanied cerebellar ataxia. These diseases can be further broken down into discrete groups according to their underlying molecular genetic cause. The most common are the polyglutamine ataxias, of which there are six; Spinocerebellar ataxia type 1, 2, 3, 6, 7 and 17. These diseases are characterised by a pathological expanded cytosine-adenine-guanine (CAG) repeat sequence, in the protein coding region of a given gene. Common clinical features include lack of coordination and gait ataxia, speech and swallowing difficulties, as well as impaired hand and motor functions. The polyglutamine spinocerebellar ataxias are typically late onset diseases that are progressive in nature and often lead to premature death, for which there is currently no known cure or effective treatment strategy. Although caused by the same molecular mechanism, the causative gene and associated protein differ for each disease. The exact mechanism by which disease pathogenesis is caused remains elusive. However, the variable (CAG) n repeats are codons that may be translated to an expanded glutamine tract, leading to conformational changes in the protein, giving it a toxic gain of function. Several pathogenic pathways have been implicated in polyglutamine spinocerebellar ataxia diseases, such as the hallmark feature of neuronal nuclear inclusions, protein misfolding and aggregation, as well as transcriptional dysregulation. These pathways are attractive avenues for potential therapeutic interventions, as the potential to treat more than one disease exists. Research is ongoing, and several promising therapies are currently underway in an attempt to provide relief for this devastating class of diseases.. However, mutations can arise de novo, through errors in DNA replication such that two genetically healthy parents can give rise to an affected child.There are currently six characterised polyQ SCAs (1, 2, 3, 6, 7 and 17) (Table 1), and together with three other diseases, namely Huntington's disease, spinal and bulbar muscular atrophy and dentatorubropallidoluysian atrophy (DRPLA), form a larger category of polyQ diseases [7][8][9][10]. Th ere is little relief for individuals suffering from polyQ SCA disorders, with symptomatic treatments the only available option. Long term pharmacological treatment, although admirable, tends to fall short in an effective management strategy, as unwanted complications and low drug efficacy still exist. In addition, none of these diseases have any treatments that slow the progression of the disease; leaving affected individuals with the daunting reality that time may be a severe limiting factor. Several experimental approaches are currently being assessed to overcome these difficulties. This review will focus on the clinical and molecular features of polyQ SCA diseases (which will be referred to as SCA diseases), as well as highlight several promising and emerging therapeutic strategies...

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“…Brainstem oculomotor signs such as saccadic slowing or ophthalmoparesis are observed in 74% (Schmitz-Hübsch, et al, 2008). Reduction of saccade velocity can be detected in mildly affected patients and it is accentuated with the disease duration.…”

Section: Spinocerebellar Ataxia Type 1 (Sca1)mentioning

confidence: 99%

Eye Movement Abnormalities in Spinocerebellar Ataxias

Rodríguez‐Labrada¹,

Velázquez‐Pérez²

2012

Spinocerebellar Ataxia

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Spinocerebellar ataxia types 1, 2, 3, and 6

Abstract: Our study suggests that spinocerebellar ataxia (SCA) 1, SCA2, and SCA3 share a number of common biologic properties, whereas SCA6 is distinct in that its phenotype is more determined by age than by disease-related factors.

Cited by 243 publications

References 21 publications

Quantitative Assessment of Brain Stem and Cerebellar Atrophy in Spinocerebellar Ataxia Types 3 and 6: Impact on Clinical Status

Quantitative Assessment of Brain Stem and Cerebellar Atrophy in Spinocerebellar Ataxia Types 3 and 6: Impact on Clinical Status

Polyglutamine ataxias: From Clinical and Molecular Features to Current Therapeutic Strategies

Eye Movement Abnormalities in Spinocerebellar Ataxias

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