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Deep into the machinery of adult fragile X
Date:8/15/2007

Researchers have reported new insight into the pathology underlying a recently identified neurological disorder that strikes middle-aged adults that is caused by alterations in the same gene that causes fragile X syndrome. Fragile X tremor/ataxia syndrome (FXTAS) overwhelmingly affects males, usually in their 50s, causing Parkinsons-like symptoms and cognitive decline. In contrast, fragile X syndrome manifests itself from birth and is the most common form of X-linked mental retardation.

In two related papers in the August 16, 2007, issue of the journal Neuron, published by Cell Press, researchers report studies revealing how FXTAS might arise from malfunction of the same gene that causes fragile X syndrome.

They theorize that the mutation causing FXTAS likely triggers a failure of the mechanism for transporting the genetic material messenger RNA within neurons to protein-making sites. The result, they theorize, is a lethal clogging of brain cells.

One paper was authored by a research team led by Stephen Warren, and the other by researchers led by co-senior authors David Nelson and Juan Botas.

FXTAS, like fragile X syndrome, is produced by a mutation in the fragile X mental retardation gene, FMR1. However, unlike fragile X syndrome, in which the mutation causes complete loss of the genes functions, the FXTAS mutation produces a different, more subtle abnormality. Both mutations cause the FMR1 gene to stutter, that is to have abnormally long strings of repeats of the same sequence of three genetic units, called nucleotides. However, while the fragile X mutation produces more than 200 repeats, causing loss of function, the FXTAS mutation produces between 55 and 200 repeats, versus fewer than 55 repeats for most unaffected people.

These repeats in the mutant DNA gene are copied onto the messenger RNA that carries genetic information from the nucleus to the protein-making machinery. A central puzzle has been how the strin
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Contact: Nancy Wampler
nwampler@cell.com
617-386-2121
Cell Press
Source:Eurekalert

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