Ataxin-1 and ataxin-2 intermediate-length PolyQ expansions in amyotrophic lateral sclerosis

Institute of Neurology (W.S., P.V., F.B., A.G.), University Magna Graecia, Catanzaro
Neurology (Impact Factor: 8.29). 11/2012; 79(24). DOI: 10.1212/WNL.0b013e318278b618
Source: PubMed


Recent evidence suggests that intermediate-length polyglutamine (PolyQ) expansions in the ataxin-2 (ATXN-2) gene are a risk factor for amyotrophic lateral sclerosis (ALS). This work was undertaken with the aim to investigate the frequency of ataxin-1 (ATXN-1) and ATXN-2 PolyQ expansions in a cohort of patients with sporadic ALS (sALS) and patients with familial ALS (fALS) from southern Italy.

We assessed the PolyQ lengths of ATXN-1 and ATXN-2 in 405 patients with sALS, 13 patients with fALS, and 296 unrelated controls without history of neurodegenerative disorders.

We found significantly higher intermediate PolyQ expansions ≥ 32 for ATXN-1 alleles and ≥ 28 for ATXN-2 alleles in the sALS cohort (ATXN-1: ALS, 7.07% vs controls, 2.38%; p = 0.0001; ATXN-2: ALS, 2.72% vs controls, 0.5%; p = 0.001). ATXN-1 CAT and ATXN-2 CAA interruptions were detected in patients with ALS only. Age at onset, site of onset, and sex were not significantly related to the ATXN-1 or ATXN-2 PolyQ repeat length expansions.

Both ATXN-1 and ATXN-2 PolyQ intermediate expansions are independently associated with an increased risk for ALS.

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Available from: Giancarlo Logroscino, Dec 30, 2013
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    • "The initial study focused on the range 27–33 in the number of CAG repeats, and determined this range as an intermediate CAG (PolyQ) repeat using ROC curves. However, no consensus has been reached regarding which CAG repeat range is associated with ALS [43], [48], [52], [65]. "
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