Phenotype Characterization of HD Intermediate Alleles in PREDICT-HD

J Huntingtons Dis. 2016 Dec 15;5(4):357-368. doi: 10.3233/JHD-160185.


Background: Huntington disease (HD) is a neurodegenerative disease caused by a CAG repeat expansion on chromosome 4. Pathology is associated with CAG repeat length. Prior studies examining people in the intermediate allele (IA) range found subtle differences in motor, cognitive, and behavioral domains compared to controls.

Objective: The purpose of this study was to examine baseline and longitudinal differences in motor, cognitive, behavioral, functional, and imaging outcomes between persons with CAG repeats in three ranges: normal (≤26), intermediate (27-35), and reduced penetrance (36-39).

Methods: We examined longitudinal data from 389 participants in three allele groups: 280 normal controls (NC), 21 intermediate allele [IA], and 88 reduced penetrance [RP]. We used linear mixed models to identify differences in baseline and longitudinal outcomes between groups. Three models were tested: 1) no baseline or longitudinal differences; 2) baseline differences but no longitudinal differences; and 3) baseline and longitudinal differences.

Results: Model 1 was the best fitting model for most outcome variables. Models 2 and 3 were best fitting for some of the variables. We found baseline and longitudinal trends of declining performance across increasing CAG repeat length groups, but no significant differences between the NC and IA groups.

Conclusion: We did not find evidence to support differences in the IA group compared to the NC group. These findings are limited by a small IA sample size.

Keywords: Huntington disease; intermediate alleles.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles*
  • Analysis of Variance
  • Corpus Striatum / diagnostic imaging
  • Female
  • Follow-Up Studies
  • Humans
  • Huntington Disease / diagnostic imaging
  • Huntington Disease / genetics*
  • Huntington Disease / physiopathology*
  • Huntington Disease / psychology
  • Internationality
  • Linear Models
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Motor Activity
  • Neuropsychological Tests
  • Phenotype
  • Prospective Studies
  • Young Adult