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

Abstract

OBJECTIVE:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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

• Authors: Francesca L Conforti, Rossella Spataro, William Sproviero, Rosalucia Mazzei, Francesca Cavalcanti, Francesca Condino, Isabella L Simone, Giancarlo Logroscino, Alessandra Patitucci, Angela Magariello, Maria Muglia, Carmelo Rodolico, Paola Valentino, Francesco Bono, Tiziana Colletti, Maria R Monsurrò, Antonio Gambardella, Vincenzo La Bella
• Journal: Neurology (Neurology) Vol. 79 Issue 24 Pg. 2315-20 (Dec 11 2012) ISSN: 1526-632X [Electronic] United States
• PMID: 23197749 (Publication Type: Journal Article)

Chemical References

• ATXN1 protein, human
• Ataxin-1
• Ataxins
• Nerve Tissue Proteins
• Nuclear Proteins
• Peptides
• polyglutamine

Topics

• Adult
• Age Factors
• Age of Onset
• Aged
• Aged, 80 and over
• Alleles
• Amyotrophic Lateral Sclerosis (genetics)
• Ataxin-1
• Ataxins
• Female
• Genetic Predisposition to Disease
• Genotype
• Humans
• Italy
• Male
• Middle Aged
• Nerve Tissue Proteins (genetics)
• Nuclear Proteins (genetics)
• Peptides (genetics)
• Risk Factors
• Trinucleotide Repeat Expansion