Spinocerebellar ataxia type 7 in South Africa: Epidemiology, pathogenesis and therapy

Watson, Lauren M.; Smith, Danielle C.; Scholefield, Janine; Ballo, Robea; Kidson, Susan H.; Greenberg, L J; Wood, Matthew

doi:10.7196/samj.2016.v106i6.11010

Cited by 6 publications

(7 citation statements)

References 25 publications

(27 reference statements)

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“…This figure increases again when considering the native African population, in whom SCA7 represents 59% of all SCA diseases, while SCA3 only represents 1% [84]. In fact, distribution of SCAs in South Africa as a whole, drastically differs from that elsewhere [78,84].…”

Section: Prevalence and Incidencementioning

confidence: 83%

“…With regards to SCA3, the prevalence is at its highest in Brazil (69% of SCA cases), Portugal (58%) and China (49%) and relatively low in USA (21%), India (3%) and Italy (1%) [77,[79][80][81][82][83]. An interesting case is the founder effect of SCA7 in South Africa, where this disease represents 26.6% of SCA diseases [84], a figure that is significantly higher than the 2% occurrence worldwide [78]. This figure increases again when considering the native African population, in whom SCA7 represents 59% of all SCA diseases, while SCA3 only represents 1% [84].…”

Section: Prevalence and Incidencementioning

confidence: 99%

“…The epidemiological data available about the prevalence of SCA diseases is limited, and most likely does not represent an accurate occurrence, due to the high degree of variation between difference populations and ethnic backgrounds. Founder effects are seen in Cuba (particularly those of Spanish decent), Portugal and South Africa in SCA2, SCA3 and SCA7, respectively [47,[76][77][78]. Several geographically localised studies have been conducted on the prevalence of ADCAs, with the focus on the six SCA diseases.…”

Section: Prevalence and Incidencementioning

confidence: 99%

“…SCA7 is typically the only SCA where affected individuals go completely blind (Table 1) [111]. SCA7 retinal pathology initially affects the cones, with progression to the rod photoreceptors, although cones are found to be more severely affected [78]. The initial sign of retinal degeneration is dyschromatopia in the blue-yellow axis [169].…”

Section: Sca7 Clinical Featuresmentioning

confidence: 99%

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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: Prevalence and Incidencementioning

confidence: 83%

Section: Prevalence and Incidencementioning

confidence: 99%

Section: Prevalence and Incidencementioning

confidence: 99%

Section: Sca7 Clinical Featuresmentioning

confidence: 99%

See 2 more Smart Citations

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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show abstract

“…[3] There was minimal evidence at the time that some inherited blinding conditions result from a primary insult to the retinal pigment epithelium (RPE) and not to the neural retina, as had been shown for other blinding conditions. But the decision to work on the RPE has been fortunate and productive.…”

Section: Research Collaborations Between Human Genetics and Cell Biologymentioning

confidence: 99%

The rise of developmental genetics – a historical account of the fusion of embryology and cell biology with human genetics and the emergence of the Stem Cell Initiative

2016

Self Cite

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Founder Effects of Spinocerebellar Ataxias in the American Continents and the Caribbean

Rodríguez‐Labrada¹,

Martins

Magaña³

et al. 2020

Cerebellum

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Spinocerebellar ataxia type 7 in South Africa: Epidemiology, pathogenesis and therapy

Cited by 6 publications

References 25 publications

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

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

The rise of developmental genetics – a historical account of the fusion of embryology and cell biology with human genetics and the emergence of the Stem Cell Initiative

Founder Effects of Spinocerebellar Ataxias in the American Continents and the Caribbean

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