Prevalence of Huntington's disease gene CAG repeat alleles in sporadic amyotrophic lateral sclerosis patients

Abstract

A higher prevalence of intermediate ataxin-2 CAG repeats in amyotrophic lateral sclerosis (ALS) patients has raised the possibility that CAG expansions in other polyglutamine disease genes could contribute to ALS neurodegeneration. We sought to determine whether expansions of the CAG repeat of the HTT gene that causes Huntington's disease, are associated with ALS. We compared the HTT CAG repeat length on a total of 3144 chromosomes from 1572 sporadic ALS patients and 4007 control chromosomes, and also tested its possible effects on ALS-specific parameters, such as age and site of onset and survival rate. Our results show that the CAG repeat in the HTT gene is not a risk factor for ALS nor modifies its clinical presentation. These findings suggest that distinct neuronal degeneration processes are involved in these two different neurodegenerative disorders.

Key words::

• Huntington's disease
• amyotrophic lateral sclerosis
• trinucleotide repeat
• neurodegenerative disease
• polyglutamine expansion

Acknowledgements

The authors wish to thank Lucie Bruijn of the ALS Association, Seung Kwak, David Howland and Jamshid Arjomand of CHDI Foundation for enabling the study.

EMR is the recipient of a scholarship from Fundação para a Ciência e a Tecnologia. Grants were received from the National Institutes of Health NINDS Huntington’s Disease Center Without Walls (JFG, MEM) and the CHDI Foundation, Inc. (JFG, MEM). Generous support was provided by the ALS Therapy Alliance, Project ALS, the Angel Fund, the Pierre L. de Bourgknecht ALS Research Foundation, the Al-Athel ALS Research Foundation, the ALS Family Charitable Foundation and the National Institute of Neurological Disorders and Stroke (RHB). JEL acknowledges grant support from NIH/NINDS. NT and VS have been supported by a Francesco Caleffidonation and acknowledge grant support from AriSLA and the Italian Ministry of Health, Ricerca Finalizzata, 2009.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.