Neurology

Answer 6 Trinucleotide repeat expansion. Huntington’s disease, 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 Huntington’s disease with an affected father.13 REFERENCES 11. Kremer B, Goldberg P, Andrew SE, et al. A worldwide study of the Huntington’s 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 Huntington’s 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. Click here to return to the questions

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