scholarly journals Non-Mendelian Genetic Aspects in Spinocerebellar Ataxias (SCAS): The Case of Machado-Joseph Disease (MJD)

10.5772/30319 ◽  
2012 ◽  
Author(s):  
Manuela Lima ◽  
Jcome Bruges-Armas ◽  
Conceio Bettencourt
Keyword(s):  
Spinocerebellar Ataxias ◽  
Machado Joseph Disease ◽  
Mendelian Genetic

scholarly journals Machado-Joseph disease mutations as the genetic basis of most spinocerebellar ataxias in Germany.

1995 ◽  
Vol 59 (4) ◽  
pp. 449-450 ◽  
Author(s):  
L Schols ◽  
G Amoiridis ◽  
M Langkafel ◽  
T Buttner ◽  
H Przuntek ◽  
...  
Keyword(s):  
Genetic Basis ◽  
Spinocerebellar Ataxias ◽  
Disease Mutations ◽  
Machado Joseph Disease

scholarly journals Machado-Joseph disease in Brazil: from the first descriptions to the emergence as the most common spinocerebellar ataxia

2012 ◽  
Vol 70 (8) ◽  
pp. 630-632 ◽  
Author(s):  
José Luiz Pedroso ◽  
Pedro Braga-Neto ◽  
João Radvany ◽  
Orlando Graziani Povoas Barsottini
Keyword(s):  
Nervous System ◽  
Spinocerebellar Ataxia ◽  
Autosomal Dominant ◽  
Pathophysiological Mechanism ◽  
Spinocerebellar Ataxias ◽  
Specific Therapy ◽  
Genetic Characteristics ◽  
New Knowledge ◽  
Machado Joseph Disease ◽  
First Descriptions

Machado-Joseph disease is an autosomal dominant inherited disorder of Azorean ancestry firstly described in 1972. Since then, several Brazilian researchers have studied clinical and genetic issues related to the disease. Nowadays, Machado-Joseph disease is considered the most common spinocerebellar ataxia worldwide. Machado-Joseph disease still has no specific therapy to arrest progression, but the unclear pathophysiological mechanism, features related to genetic characteristics, phenotype variability, apparently global involvement of the nervous system in the disease and the therapeutic challenges continue to attract investigators in the field of spinocerebellar ataxias. Brazilian researchers have distinguished themselves in the ongoing investigation seeking new knowledge about Machado-Joseph disease.

scholarly journals Eyelid retraction is not a pathognomonic sign of Machado-Joseph disease in the context of spinocerebellar ataxias

2014 ◽  
Vol 72 (4) ◽  
pp. 326-327
Author(s):  
José Luiz Pedroso ◽  
Paulo Victor Sgobbi de Souza ◽  
Wladimir Bocca Vieira de Rezende Pinto ◽  
Marcus Vinicius Cristino Albuquerque ◽  
Orlando G. P. Barsottini
Keyword(s):  
Spinocerebellar Ataxias ◽  
Eyelid Retraction ◽  
Machado Joseph Disease ◽  
Pathognomonic Sign

scholarly journals Molecular characteristics of Machado-Joseph disease mutation in 25 newly described Brazilian families

1997 ◽  
Vol 20 (4) ◽  
pp. 717-724 ◽  
Author(s):  
Iscia Lopes-Cendes ◽  
Hélio G.A. Teive ◽  
Francisco Cardoso ◽  
Erika M. Viana ◽  
Maria E. Calcagnotto ◽  
...  
Keyword(s):  
Late Onset ◽  
Age At Onset ◽  
Collaborative Study ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Causative Mutation ◽  
Molecular Characteristics ◽  
Spinocerebellar Ataxias ◽  
Extrapyramidal Signs ◽  
Machado Joseph Disease

Machado-Joseph disease (MJD) is a form of autosomal dominant spinocerebellar ataxia first described in North-American patients originating from the Portuguese islands of the Azores. Clinically this disorder is characterized by late onset progressive ataxia with associated features, such as: ophthalmoplegia, pyramidal and extrapyramidal signs and distal muscular atrophies. The causative mutation is an expansion of a CAG repeat in the coding region of the MJD1 gene. We have identified 25 unrelated families segregating the MJD mutation during a large collaborative study of spinocerebellar ataxias in Brazil. In the present study a total of 62 family members were genotyped for the CAG repeat in the MJD1 gene, as well as 63 non-MJD individuals (126 normal chromosomes), used as normal controls. We observed a wide gap between the size range of the normal and expanded CAG repeats: the normal allele had from 12 to 33 CAGs (mean = 23 CAGs), whereas the expanded alleles ranged from 66 to 78 CAGs (mean = 71.5 CAGs). There were no differences in CAG tract length according to gender of affected individuals or transmitting parent. We observed a significant negative correlation between age at onset of the disease and length of the CAG tract in the expended allele (r = -0.6, P = 0.00006); however, the size of the expanded CAG repeat could explain only about 40% of the variability in age at onset (r2 = 0.4). There was instability of the expanded CAG tract during transmission from parent to offspring, both expansions and contractions were observed; however, there was an overall tendency for expansion, with a mean increase of +2.4 CAGs. The tendency for expansion appeared to the greater in paternal (mean increase of +3.5 CAGs) than in maternal transmissions (mean increase of +1.3 CAGs). Anticipation was observed in all transmissions in which ages at onset for parent and offspring were known; however, anticipation was not always associated with an increase in the expanded CAG repeat length. Our results indicate that the molecular diagnosis of MJD can be confirmed or excluded in all suspected individuals, since alleles of intermediary size were not observed.

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