Spinocerebellar ataxia type 7 associated with pigmentary retinal dystrophy

Michalik, Andrej; Martin, Jean‐Jacques; Broeckhoven, Christine Van

doi:10.1038/sj.ejhg.5201108

Cited by 139 publications

(155 citation statements)

References 83 publications

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“…Several of the SCAs have a well-documented pre-mutation range, known as incomplete penetrance. These individuals are typically asymptomatic, however due to their dynamic nature, the expansions have the ability to pass on the disease or pass on an increased CAG repeat range [68,69]. Paternally transmitted alleles are typically more unstable and prone to expansion than a maternal allele, so that diseased individuals are those who have met the pathogenic threshold for the given gene, are symptomatic and are likely to pass on a larger expansion [69,70].…”

Section: Genetic Testingmentioning

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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Section: Genetic Testingmentioning

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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“…The mean age at onset ranged from 40 to 50 years of age (9)(10)(11) (12). In past reports of SCA7, macular degeneration has been the main clinical feature (8,13 …”

Section: F I G U R E 3 F U N D U S C O P Y F I N D I N G S A: F Amentioning

confidence: 99%

Unusual Retinal Phenotypes in an SCA7 Family

et al. 2009

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“…La situation est très différente pour des stimulus symboliques tels que des mots. En effet on sait que leur lecture implique un certain nombre d'étapes corticales permettant leur reconnaissance et l'accès à leur sens [6]. Qu'en est-il lorsque ces mots ne sont pas consciemment perçus ?…”

Section: Nouvelleunclassified

“…Ataxie spinocérébelleuse de type 7 et atteinte rétinienne D'autre part, SCA7 est la seule maladie par expansion de polyglutamine dans laquelle la rétine est atteinte [6]. Plusieurs groupes ont analysé la toxicité de l'ATXN7 mutée dans la rétine de souris transgéniques et identifié des anomalies transcriptionnelles reproductibles entre les différents modèles utilisés [7][8][9].…”

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