Human Genetics

, Volume 130, Issue 4, pp 575–580

ATXN-2 CAG repeat expansions are interrupted in ALS patients

Authors

    • Department of Medical Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD)University of Eastern Piedmont
  • Letizia Mazzini
    • Department of NeurologyA. Avogadro University and Maggiore della Carità Hospital
  • Gaia Donata Oggioni
    • Department of NeurologyA. Avogadro University and Maggiore della Carità Hospital
  • Bernadetta Luciano
    • Department of Medical Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD)University of Eastern Piedmont
  • Michela Godi
    • Department of Medical Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD)University of Eastern Piedmont
  • Alfredo Brusco
    • Department of Genetics Biology and BiochemistryUniversità degli Studi di Torino
    • S.C.d.U. Medical Genetics, A.O.U. San Giovanni Battista
  • Sandra D’Alfonso
    • Department of Medical Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD)University of Eastern Piedmont
    • Biotecnologie per la Ricerca Medica Applicata (BRMA)University of Eastern Piedmont
Original Investigation

DOI: 10.1007/s00439-011-1000-2

Cite this article as:
Corrado, L., Mazzini, L., Oggioni, G.D. et al. Hum Genet (2011) 130: 575. doi:10.1007/s00439-011-1000-2

Abstract

It has recently been suggested that short expansions of CAG repeat in the gene ATXN-2 causing SCA2 (spinocerebellar ataxia type 2) are associated with an increased risk of amyotrophic lateral sclerosis (ALS) in the populations of the USA and northern Europe. In this study, we investigated the role of ATXN-2 in Italian patients clinically diagnosed with ALS and characterized the molecular structure of ATXN-2 expansions. We assessed the size of the CAG repeat in ATXN-2 exon 1 in 232 Italian ALS patients and 395 matched controls. ATXN-2 expanded alleles containing >30 repeats have been observed in seven sporadic ALS patients (3.0%), while being absent in the controls (p = 0.00089). Four out of the seven patients had an ATXN-2 allele in the intermediate-fully pathological range: one with 32 repeats, 2 with 33 repeats and 1 with 37 repeats, accounting for 1.7% of the ALS cohort. Sequencing of expanded (>32) alleles showed that they were all interrupted with at least one CAA triplet. ATXN-2 alleles with the same length and structure have been reported in SCA2 patients with parkinsonism or in familial and sporadic Parkinson. Conversely, the phenotype of the present patients was typically ALS with no signs or symptoms of ataxia or parkinsonism. In conclusion, the findings of ATXN-2 expansions in pure ALS cases suggest that ALS may be a third phenotype (alongside ataxia/parkinsonism and pure Parkinson) associated with ATXN-2 interrupted alleles.

Copyright information

© Springer-Verlag 2011