Machado-Joseph disease in east Arnhem Land, Australia

Burt, Trevor D.; Currie, B.; Kilburn, Chandra L.; Lethlean, A.K.; Dempsey, Katherine; Blair, Ian P.; Cohen, Amnon; Nicholson, Geoffrey C.

doi:10.1212/wnl.46.4.1118

Cited by 24 publications

(16 citation statements)

References 6 publications

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“…This test provides measures of the ability to make intradimensional shifts of attention (shifts of attention within a reinforced stimulus dimension, eg, switching attention from one purple shape to another) and extradimensional shifts of attention (switching attention to previously irrelevant stimulus dimensions, eg, switching attention from shapes to lines). The ID/ ED shift task involves nine stages, with the subject proceed- SPATlAL RECOGNITION (20,23,26,27,29,301. A small target square was presented sequentially at five different locations on the computer screen, each for 2 seconds.…”

Section: Intradimensionaliextradimensional Attentional Set Shifting Tmentioning

confidence: 99%

Cognitive deficits in Machado‐Josephs disease

Maruff

Tyler

Burt

et al. 1996

Annals of Neurology

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Cognitive function was examined in 6 patients with genetically confirmed Machado-Joseph disease (MJD) and 15 age- and ethnically matched controls using a series of subtests from the Cambridge Neuropsychological Test Automated Battery (CANTAB), a touch screen-based testing system previously validated in a number of movement and neurodegenerative disorders. The MJD patients had deficits in visual attentional function that were characterized by a slowing of the processing of visual information when task demands were high and an inability to shift attention to previously irrelevant stimulus dimensions to discriminate between complex stimuli. Tests of learning and visual memory were normal. These results demonstrate that specific cognitive deficits occur in patients with MJD, independent of motor dysfunction, and these deficits may reflect disruption to frontosubcortical pathways.

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Section: Intradimensionaliextradimensional Attentional Set Shifting Tmentioning

confidence: 99%

Cognitive deficits in Machado‐Josephs disease

Maruff

Tyler

Burt

et al. 1996

Annals of Neurology

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“…The MJD type expansion mutation has not been identified in all of those Aboriginal individuals whose clinical presentation has indicated a diagnosis of the MJD type of 'Groote Syndrome' [12]. In this respect, the autosomal dominant theory of MJD causation does not fulfill Koch's postulates.…”

Section: Results Of Field Investigation Into the Origins Of The Mjd Cmentioning

confidence: 99%

“…In respect of Koch's postulates, the fact that a genealogical surveillance program failed to identify the MJD mutation in every single case of provisionally diagnosed MJD [12], suggests that other 'non genetic' eco-influences could be involved in the primary cause of the disease.…”

Section: Can a High Mn/low Mg Mineral Imbalance Account For All Facetmentioning

confidence: 99%

“…After the initial observation by Cowat in 1990 [11] that MJD ran in specific Aboriginal families, the emphasis-as to the etiology-has focussed on the likelihood of a genetic origin of MJD. The astute identification by Burt et al [12,13] of an MJD type of CAG expansion mutation in the greater majority of these victims, led to attribution solely to an autosomal dominant inheritance of an expansion mutation in the CAG repeat in chromosome 14q32.1. This implicates repercussions of carrying this mutant form of 'ataxin 3' chaperone protein in the full clinical and pathological spectrum of the MJD type of polyglutamine disease, and rejects a role of environmental factors in the pathogenesis of MJD strain of Groote syndrome.…”

Section: Introductionmentioning

confidence: 99%

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The Pathogenesis of Machado Joseph Disease: A High Manganese/Low Magnesium Initiated CAG Expansion Mutation in Susceptible Genotypes?

Purdey

2004

Journal of the American College of Nutrition

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The origin of the progressive spinocerebellar ataxic disorder 'Machado Joseph Disease (MJD)' has been attributed solely to an expansion mutation resulting from an autosomal dominant inheritance of an unstable CAG repeat in chromosome 14q32.1 of the MJD gene that encodes for the synthesis of ataxin 3. The faulty gene has purportedly been disseminated since the Middle Ages into Azorean, Dutch and Makassan communities by an international trading community based in NE-central Portugal. However, following improvements in MJD surveillance, the MJD afflicted families that have been identified in increasing numbers of familial clusters of MJD being discovered around the world--e.g. in Aboriginal, Yemenite, Asian and Japanese populations--cannot be connected back to the original Portuguese founder families, but rather implicates an environmental factor, superimposed on a genetic flaw. An analytical study of the isolated ecosystems supporting both the Portuguese and non-Portuguese MJD affected communities demonstrates a common abnormal hallmark of high manganese (Mn)/low magnesium (Mg) status, suggesting that this aberrant mineral ratio inactivates the Mn/Mg catalyzed endonuclease 1 enzyme in the biosystems of those who are dependent upon these ecosystems. Endonuclease activity is crucial for protecting against the expansion/contraction of the trinucleotide repeats in the genes that encode for proteins such as Ataxin 3--the 'mutant' chaperone protein that hallmarks the central nervous system (CNS) of MJD sufferers. It is proposed that MJD, and possibly the other more common expansion mutation diseases such as Friedrich's Ataxia and Huntingdon's Chorea, are multifactorial diseases caused by a hitherto unrecognised autosomal dominant inherited failure to regulate Mn/Mg metabolism in populations living in high Mn/low Mg ecosystems. Mg supplementation of the 'at risk' populations during the 'in utero' developmental stages could be all that is required to maintain healthy endonuclease turnover, thereby protecting MJD susceptible genotypes against this fatal, progressive neurodegenerative disease.

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“…This article addresses the third area of genetic research. Indigenous groups internationally have generally been supportive of research into rare diseases [5,6] ; however, a number of population-based research projects have generated widespread controversy. In particular, the "Vampire Project" whose researchers professed the need to sample the DNA of Indigenous groups before they vanished [7] was met with widespread criticism from Indigenous peoples.…”

Section: Genetic Variationmentioning

confidence: 99%

Personalised Medicine: A New Approach to Improving Health in Indigenous Australian Populations

Rae

Grimson

Pringle

2017

Public Health Genomics

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Personalised medicine is a newly emerging field with much to offer to all populations in improved clinical treatment options. Since the 1970s, clinicians and researchers have all been working towards improving the health of Indigenous Australians. However, there has been little research on the impact of genetics on Indigenous health, how genetic and environmental factors interact to contribute to poor health in Indigenous people, and how genetic factors specific to Indigenous people affect their responses to particular treatments. This short review highlights the urgent need for more genetic studies specific to Indigenous people in order to provide more appropriate care and to improve health outcomes. This paper explores why genetic work with Indigenous communities has been limited, how personalised medicine could benefit Indigenous communities, and highlights a number of specific instances in which personalised medicine has been critical for improving morbidity and mortality in other high-risk groups. In order to take the next step in advancing the health of Indigenous peoples, targeted research into the genetic factors behind chronic diseases is critically needed. This research may allow clinicians a better understanding of how genetic factors interact with environmental factors to influence an Indigenous Australian's individual risk of disease, prognosis, and response to therapies. It is hoped that this knowledge will produce clinical interventions that will help deliver clearly targeted, more appropriate care to this at-risk population.

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Machado-Joseph disease in east Arnhem Land, Australia

Cited by 24 publications

References 6 publications

Cognitive deficits in Machado‐Josephs disease

Cognitive deficits in Machado‐Josephs disease

The Pathogenesis of Machado Joseph Disease: A High Manganese/Low Magnesium Initiated CAG Expansion Mutation in Susceptible Genotypes?

Personalised Medicine: A New Approach to Improving Health in Indigenous Australian Populations

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