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Query: UMLS:C0039483 (giant cell arteritis)
 3,204 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Huntington's disease is associated with an expanded and unstable trinucleotide repeat (CAG)(n). Various possibilities have been suggested to explain the significance of poly-(CAG) length in HD, including changes in the structure of the product (huntingtin) which result in the protein acquiring deleterious properties. We have looked at the nucleotide sequence coding for huntingtin and find that another possibility may exist for the correlation between the occurrence of HD and poly-CAG length. We have noted an alternative reading frame that includes the trinucleotide repeat, now read as (GCA)(n). Upon close examination of this alternative gene product, we observe features that suggest it can likewise have deleterious properties.
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PMID:Does mRNA translation starting from an alternative initiation site contribute to the pathology of Huntington's disease? 1085 66

Codon reiteration disorders are caused by abnormal expansions of either polyglutamine or polyalanine tracts within the coding region of a protein. These mutations impair normal protein folding, resulting in aggregate formation in the affected tissues. Huntington's disease is the most common of the nine disorders caused by polyglutamine expansion mutations. The most extensively studied polyalanine expansion disorder is oculopharyngeal muscular dystrophy. There may be a link between diseases caused by polyglutamine and polyalanine expansion mutations as it has been shown that the expanded CAG/polyglutamine tract within the SCA3 gene can shift to the GCA[corrected]/polyalanine frame. Here, we show that this frameshifting phenomenon is more widespread and occurs in Huntington's disease. We have shown both +1 frameshift and +2 frameshift products (which may contain polyalanine or polyserine tracts, respectively) in human postmortem Huntington's disease brains and in a transgenic mouse model of Huntington's disease. Our data suggest that +1 and +2 frameshift products are generated at low levels. This may be relevant to the pathogenesis of human Huntington's disease, as we have previously shown that both polyserine and polyalanine-containing proteins are modifiers of mutant huntingtin toxicity, with low expression levels of polyalanine-containing proteins having a protective effect.
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PMID:Polyalanine and polyserine frameshift products in Huntington's disease. 1680 44