Octapeptide Repeat Insertion Mutations

Occasionally patients with a clinical phenotype typical of sCJD have other octapeptide repeat mutations, but the exact significance of these mutations in this group is unclear in many [12]. Those involving one, two or three additional repeats may be coincidental findings, as these have been found in healthy control populations [13]. Several patients with 4-OPRI insertions have been reported associated with a late-onset, short duration clinical course, often with an absence of family history and so are often mistaken for sCJD one possible explanation for this observation is discussed below. 

There are only two reports of a deletion in the repeat region (2-OPRD) in patients with CJD [18, 19]. As the 2-OPRD has not been found in healthy individuals it is likely to be a causal mutation. The 1-OPRD is an uncommon polymorphism of some healthy populations it is not known to be a susceptibility or modifying factor [20]. 

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The octapeptide repeat region is not required for the conversion of Prpc pj.pSc propagation of the disease process. Nevertheless, extra-repeat insertional mutations in one PRNP allele trigger disease. It is conceivable that disorder of copper binding in these extended protein species might feature in the formation of altered PrP isoforms and/or PrP aggregation. In this regard, it is noteworthy that PrP is... 

Fig. 2. Sequence content of spa repeats at nucleotide and amino acid levels. Repeats differing at the nucleotide level may be identical at the amino acid level. Identical codons are depicted using the same colors equivalent codons corresponding to synonymous mutations are colored with similar hues. The translated sequence reveals a conserved octapeptide motif comprised almost exclusively of charged amino acids and is suggestive of a surface-exposed loop region with repeating turns. Repeats Tl-Zl bear a single codon insertion between positions 1 and 2 most common spa types begin with one of these repeats, such that the initial repeat is usually 27-bp in length (vs. 24-bp).

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