like many other neurodegenerative disorders, is characterized by a
trinucleotide repeat expansion. The cytosine-adnenine-guanine repeat
expansion (exon 1) is translated, producing an expanded polyglutamine
tract. The size of the expansion correlates with the age of onset and,
as some have suggested, the rate of progression.11 This relationship
does not provide sufficiently precise information to have prognostic
relevance.12 The trinucleotide repeat expansion is unstable and tends
to expand with generational transmission. This instability provides a
mechanism for anticipation, resulting in an earlier age of onset in
succeeding generations. The largest expansions are seen with paternal
transmission, thus accounting for the association of juvenile-onset
Huntingtons disease with an affected father.13
- Trinucleotide repeat expansion.
11. Kremer B, Goldberg P, Andrew SE, et al. A worldwide study of the Huntingtons disease mutation. The sensitivity and specificity of measuring CAG repeats. N Engl J Med 1994;330:1401-6.
12. Lucotte G, Turpin JC, Riess O, et al. Confidence intervals for predicted age of onset, given the size of (CAG)n repeat, in Huntingtons disease. Hum Genet 1995;95:231-2.
13. Ranen NG, Stine OC, Abbott MH, et al. Anticipation and instability of IT-15 (CAG)n repeats in parent-offspring pairs with Huntington disease. Am J Hum Genet 1995;57:593-602.
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