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| GENATLAS PHENOTYPE |
| last update : 26-06-2013 |
| Symbol | MJD |
| Location | 14q32.12 |
| HGNC id | 10556 |
| Name | Machado-Joseph disease |
| Other name(s) |
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| Corresponding gene | ATXN3 |
| Other symbol(s) | SCA3 |
| Main clinical features |
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| Genetic determination | autosomal dominant |
| Related entries | including : . early onset type I with pyramidal and extrapyramidal signs . type II with cerebellar and pyramidal signs . type III with cerebellar and amyotrophic changes . type IV with parkinsonism and cerebellar disease (same gene as DOPA-responsive spinal cerebellar ataxia 3, SCA3) |
| Function/system disorder | neurology |
| Type | disease |
| Gene product |
| Name | ataxin 3 |
| Mechanism(s) |
| Gene mutation | Chromosome rearrangement | Effect | Comments |
| frameshift
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| abnormal protein/gain of function
| triplet CAG repeat amplification encoding a polyglutamine stretch (61-84), including isoforms 3c anormally expressed cytoplasmatically, but aggregating in ubiquinated intranuclear inclusions (PML/POD/ND10) where it colocalizes with proteasome, selectively in neurons of affected brain regions
| repeat expansion
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| abnormal protein/gain of function
| associated with polyQ-expanded gene product, negatively correlated with the age of disease onset
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| Remark(s) |
. may be 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 (Purdey 2004)
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