title: Characterization of a large group of individuals with huntington disease and their relatives enrolled in the COHORT study.
abstract: BACKGROUND
  Careful characterization of the phenotype and genotype of Huntington disease (HD) can foster better understanding of the condition.
  
  
  METHODS
  We conducted a cohort study in the United States, Canada, and Australia of members of families affected by HD. We collected demographic and clinical data, conducted the Unified Huntington's Disease Rating Scale and Mini-Mental State Examination, and determined Huntingtin trinucleotide CAG repeat length. We report primarily on cross-sectional baseline data from this recently completed prospective, longitudinal, observational study.
  
  
  RESULTS
  As of December 31, 2009, 2,318 individuals enrolled; of these, 1,985 (85.6%) were classified into six analysis groups. Three groups had expanded CAG alleles (36 repeats or more): individuals with clinically diagnosed HD [n = 930], and clinically unaffected first-degree relatives who had previously pursued [n = 248] or not pursued [n = 112] predictive DNA testing. Three groups lacked expanded alleles: first-degree relatives who had previously pursued [n = 41] or not pursued [n = 224] genetic testing, and spouses and caregivers [n = 430]. Baseline mean performance differed across groups in all motor, behavioral, cognitive, and functional measures (p<0.001). Clinically unaffected individuals with expanded alleles weighed less (76.0 vs. 79.6 kg; p = 0.01) and had lower cognitive scores (28.5 vs. 29.1 on the Mini Mental State Examination; p = 0.008) than individuals without expanded alleles. The frequency of "high normal" repeat lengths (27 to 35) was 2.5% and repeat lengths associated with reduced penetrance (36 to 39) was 2.7%.
  
  
  CONCLUSIONS
  Baseline analysis of COHORT study participants revealed differences that emerge prior to clinical diagnosis. Longitudinal investigation of this cohort will further characterize the natural history of HD and genetic and biological modifiers.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT00313495.
authors.affiliation: Department of Neurology, Johns Hopkins Medicine, Baltimore, Maryland, United States of America. ray.dorsey@jhmi.edu
authors.forename: E  Ray
authors.initials: E
authors.lastname: Dorsey
mesh_terms: D000483:Alleles; D001315:Australia / Q000453:epidemiology; D002170:Canada / Q000453:epidemiology; D015331:Cohort Studies; D005190:Family; D005820:Genetic Testing / Q000706:statistics & numerical data*; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000453:epidemiology* / Q000235:genetics*; D008137:Longitudinal Studies; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D011446:Prospective Studies; D018911:Trinucleotide Repeats; D014481:United States / Q000453:epidemiology
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins