TORNA ALL’ELENCO

Atxn2polyq intermediate repeat is a modifier of ALS phenotype in a population based study in Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

2014
AOU Città della Salute di Torino

Tipo pubblicazione

Conference Abstract

Autori/Collaboratori (20)Vedi tutti...

Calvo A

Moglia C

Canosa A


et alii...

Abstract

Background: An intermediate-length (CAG) expansion (encoding 27 - 33 glutamines, polyQ) in ataxin 2 (ATXN2) gene, already known as the cause of spinocerebellar ataxia type 2 (SCA2), has been found to be related to an increased risk of developing ALS. The clinical characteristics of patients with this expansion remain poorly investigated. Objectives: The aim of this study was to analyze the frequency of intermediate polyQ expansion in the ATXN2 gene in a population-based cohort of Italian patients (discovery cohort), with an in-depth assessment of their clinical and prognostic characteristics, and to replicate the findings in an independent cohort of consecutive patients from an ALS tertiary center (validation cohort). We assessed survival of patients with ATXN2 polyQ expansion compared with patients with normal length expansion. Methods: PolyQ expansions were assessed in 672 patients incident in Piemonte and Valle d'Aosta regions, Italy, during the 6-year period from 2007 to 2012 (discovery cohort); controls were 509 neurologically healthy subjects, resident in the study area, age- and gender-matched to cases. The validation cohort includes 661 patients consecutively admitted between 2001and 2013 in the ALS Clinic Centre of the Catholic University in Rome, Italy. Diagnostic criteria were identical to those of the discovery cohort. Genomic DNA was isolated from peripheral blood lymphocytes using a standard protocol. The ATXN-2 CAG repeat in exon 1 was amplified using a fluorescent primer and sized by capillary electrophoresis on an ABI 3130 genetic analyzer. We considered as cut-off a repeat size ? 31. All ALS cases of both cohorts were also tested for SOD1 , TARDBP , FUS , ANG and C9ORF72 . Familial ALS patients were also tested for OPTN . Results: In the discovery cohort the frequency of ? 31 polyQ ATNX2 repeats was significantly more common in ALS cases (19 patients vs. 1 control, p = 0.0001; odds ratio 14.8, 95% confidence interval, 1.9 - 110.8). Patie

DOI : 10.3109/21678421.2014.960179/147

Keywords

polyglutamine; glutamine; antisense oligonucleotide; genomic DNA; nuclease; DNA; population; phenotype; human; patient; survival; X ray bone densitometer; Italy; risk; gene; Tertiary (period); diagnosis; university; hospital; normal human; spinocerebellar degeneration; gender; risk factor; confidence interval; genetic analyzer; capillary electrophoresis; exon; CAG repeat; peripheral lymphocyte; therapy; clustered regularly interspaced short palindromic repeat;