{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:04:24Z","timestamp":1791295464818,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2007,1,29]],"date-time":"2007-01-29T00:00:00Z","timestamp":1170028800000},"content-version":"vor","delay-in-days":28,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2007,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Friedreich's ataxia patients are homozygous for expanded alleles of a GAA triplet\u2010repeat sequence in the <jats:italic>FXN<\/jats:italic> gene. Patients develop progressive ataxia due to primary neurodegeneration involving the dorsal root ganglia (DRGs). The selective neurodegeneration is due to the sensitivity of DRGs to frataxin deficiency; however, the progressive nature of the disease remains unexplained. Our objective was to test whether the expanded GAA triplet\u2010repeat sequence undergoes further expansion in DRGs as a possible mechanism underlying the progressive pathology seen in patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Small\u2010pool polymerase chain reaction analysis, a sensitive technique that allows the measurement of repeat length in individual <jats:italic>FXN<\/jats:italic> genes, was used to analyze somatic instability of the expanded GAA triplet\u2010repeat sequence in multiple tissues obtained from six autopsies of Friedreich's ataxia patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>DRGs showed a significantly greater frequency of large expansions (<jats:italic>p<\/jats:italic> &lt; 0.001) and a relative paucity of large contractions compared with all other tissues. There was a significant age\u2010dependent increase in the frequency of large expansions in DRGs, which ranged from 0.5% at 17 years to 13.9% at 47 years (<jats:italic>r<\/jats:italic> = 0.78; <jats:italic>p<\/jats:italic> = 0.028).<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Progressive pathology involving the DRGs is likely due to age\u2010dependent accumulation of large expansions of the GAA triplet\u2010repeat sequence. Thus, somatic instability of the expanded GAA triplet\u2010repeat sequence may contribute directly to disease pathogenesis and progression. Progressive repeat expansion in specific tissues is a common theme in the pathogenesis of triplet\u2010repeat diseases. Ann Neurol 2007;61:55\u201360<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.21052","type":"journal-article","created":{"date-parts":[[2007,2,2]],"date-time":"2007-02-02T19:14:16Z","timestamp":1170443656000},"page":"55-60","source":"Crossref","is-referenced-by-count":110,"title":["Progressive gaa expansions in dorsal root ganglia of Friedreich's ataxia patients"],"prefix":"10.1002","volume":"61","author":[{"given":"Irene","family":"De 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