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Clinical characteristics–motor phenotype
I02 Effect of CAG length on motor scores of children at risk for huntington's disease
  1. P Nopoulos1,
  2. K Mathews1,
  3. J Paulsen1,
  4. E Epping1,
  5. A Conrad1,
  6. J Perlmutter2,
  7. B Schlaggar2
  1. 1University of Iowa, Iowa City, Iowa, USA
  2. 2Washington University, St. Louis, Missouri, USA

Abstract

Background Simple sequence repeats such as triple repeats in the genome are dynamic mutations that contribute to normal variation in behavioural traits, but when expanded beyond a threshold, cause neurologic disease. In the case of HD, the effects of CAG repeat have often been studied in the context of gene-expansion, however the effects of CAG repeat on brain function in the normal range have not been studied. The KidsHD program evaluates children (ages 6–18 years) who are at risk for HD (no children manifesting symptoms, no JHD included). For research purposes only, participants are genotyped and separated into gene-expanded (GE) and those that are non gene-expanded (GNE). This sample provides a rich opportunity to study the entire spectrum of CAG repeat length in relationship to a specific brain function—motor skills.

Methods The Physical and Neurological Evaluation of Subtle Signs (PANESS) is a standardised assessment of fine and gross motor coordination. Higher scores indicate poorer motor coordination. Skilled raters (blind to gene status) evaluated each participant. A total of 35 GNE (CAG range 15–34) and 34 GE (CAG range 39–59) participants were assessed. Pearson Correlations controlling for age and sex were calculated to evaluate the relationship between length of CAG repeat and PANESS scores.

Results In the GNE group, there was a significant negative correlation indicating that the greater the CAG repeat, the better the motor coordination, r=−0.39, p=0.02. In the GE group, there was a significant positive correlation, r=0.37, p=0.03 indicating that the higher the CAG repeat, the worse the motor coordination.

Conclusions Length of CAG repeat in the Huntintin gene is directly related to motor performance in both normal and expanded ranges. The relationship between CAG repeat in the normal range supports the notion that this type of dynamic mutation serves an important function in modulating brain development and function.

  • Prodromal
  • motor coordination
  • children at risk

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