CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion
Year: 2012
Type: article
Abstract: We read with interest the article by Lee et al. 1 concerning the potential effect of the CAG repeat size in the normal HTT allele on age at motor onset in Huntington disease (HD).Although the authors have done an excellent job in analyzing data on an impressively large number of patients with HD, we feel that the following points should be considered before dismissing a potential disease-modifying role of the normal HTT allele.First, the authors' findings concern age at motor onset only yet cognitive and behavioral disturbances often precede motor onset and should be treated equally in defining age at onset as in our study.2 Second, the authors equate age at motor onset to rate of disease progression, 1 and do not formally assess serial clinical measurements on the same individuals as we previously reported.2 However, the observation that, despite a similar age at onset, homozygote patients display a faster rate of clinical deterioration suggests that mechanisms contributing to age at onset and disease progression might not entirely overlap.3 Third, although excluding outliers generally yields more robust statistical models, this comes at the cost of missing potentially interesting genetic modifiers at the allelic extremes.4
Source: Neurology
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2782009717