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

6533b870fe1ef96bd12cf1e0

RESEARCH PRODUCT

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

Giancarlo Logroscino A. Magariello Francesca Cavalcanti Francesco Bono Isabella Laura Simone Rossella Spataro Antonio Gambardella M. R. Monsurrò Rosalucia Mazzei William Sproviero V. La Bella Francesca Condino Maria Muglia Paola Valentino Carmelo Rodolico Francesca Luisa Conforti Alessandra Patitucci T. Colletti

subject

Oncology Adult Male medicine.medical_specialty Genotype ALS; ATXN-1; ATXN-2 Ataxin 1 Nerve Tissue Proteins Risk Factors Internal medicine medicine Humans In patient Genetic Predisposition to Disease Amyotrophic lateral sclerosis Allele Risk factor Age of Onset ATXN-2 ATXN-1 Alleles Ataxin-1 Aged Aged 80 and over biology business.industry Amyotrophic Lateral Sclerosis Age Factors Nuclear Proteins Middle Aged medicine.disease Increased risk POLYGLUTAMINE EXPANSIONS; HEXANUCLEOTIDE REPEAT; ALS; TYPE-1; NEURODEGENERATION; PHENOTYPE; GENETICS; PROTEIN; C9ORF72; RISK Ataxins Italy Ataxin Cohort biology.protein Female Settore MED/26 - Neurologia Neurology (clinical)ALS business Peptides Trinucleotide Repeat Expansion

description

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.

year	journal	country	edition	language
2012-01-01

http://hdl.handle.net/10447/75975