ATAXIN2 CAG-repeat length in Italian patients with amyotrophic lateral sclerosis: Risk factor or variant phenotype? Implication for genetic testing and counseling

Cinzia Gellera, Nicola Ticozzi, Viviana Pensato, Lorenzo Nanetti, Alessia Castucci, Barbara Castellotti, Giuseppe Lauria, Franco Taroni, Vincenzo Silani, Caterina Mariotti

Research output: Contribution to journalArticle

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease mainly involving cortical and spinal motor neurons. Several studies indicated that intermediate CAG expansions in ataxin-2 gene (. ATXN2) are associated with increased risk of ALS. We analyzed . ATXN2 CAG repeats in 658 sporadic ALS patients (SALS), 143 familial ALS cases (FALS), 231 sporadic ataxic subjects, and 551 control subjects. The frequency of . ATXN2 alleles with 27-30 repeats was similar in SALS and control subjects. Fifteen SALS subjects carried ≥ 31 CAG repeats. This difference was statistically significant (. p = 0.0014). No alleles with ≥ 34 CAG were found. In FALS, the distribution of . ATXN2 alleles was similar to control subjects. Our results further contributed in refining CAG-repeat range significantly associated with sporadic ALS. Literature data and our findings indicate that only alleles with ≥ 31 CAG may represent low-penetrance disease/susceptibility alleles associated with variable neurodegenerative phenotypes, including cerebellar ataxia, parkinsonism, and ALS. Overlapping phenotypes should be considered in genetic testing and counseling, both for patients and at-risk family members.

Original languageEnglish
JournalNeurobiology of Aging
Volume33
Issue number8
DOIs
Publication statusPublished - Aug 2012

Keywords

  • Amyotrophic lateral sclerosis
  • Ataxin 2
  • ATXN2
  • CAG
  • Neurodegenerative disorders
  • Polyglutamine disorders
  • Spinocerebellar ataxia type 2
  • Triplet repeats

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Ageing
  • Developmental Biology
  • Geriatrics and Gerontology

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