Does trans size matter in Huntington disease?

Abstract

Huntington disease (HD) is a progressive neurodegenerative disorder resulting in involuntary movements with psychiatric and cognitive dysfunction. HD is caused by a polyglutamine repeat within the HTT protein and is inherited in an autosomal dominant pattern.1,2 Although generally considered an archetypal monogenic disorder, there remains a high degree of phenotypic heterogeneity among patients with HD, particularly with respect to age at onset of motor manifestations. The length of the expanded repeat allele affects presentation and correlates with age at onset of motor manifestations, although this alone does not explain the variance that is observed.3,4 Therefore studies are ongoing to identify other genetic disease modifiers that may provide alternative therapeutic targets. In this issue of Neurology ®, the study of Lee et al.5 attempts to address the question of whether the size of the HTT repeat on the trans allele affects the age at onset of motor symptoms. This study represents a response to the study by Aziz et al.,6 published in the October 20, 2009, issue of Neurology , which suggested that the mutant and normal alleles interact with both repeat lengths determining age at onset and therefore apparent penetrance. The earlier study examined age at onset in 921 patients with …