title: Characterization of the Huntington intermediate CAG repeat expansion phenotype in PHAROS.
abstract: OBJECTIVE
  We aimed to describe the clinical phenotype conferred by the intermediate-length huntingtin allele CAG repeat expansion in a population-based study.
  
  
  METHODS
  The Prospective Huntington At Risk Observational Study (PHAROS) enrolled adults at risk for Huntington disease (HD). They were assessed approximately every 9 months with the Unified Huntington's Disease Rating Scale (UHDRS) by investigators unaware of participants' gene status. UHDRS scores were compared according to the Huntingtin gene CAG repeat number: expanded >36, intermediate 27-35, and nonexpanded controls <26.
  
  
  RESULTS
  Fifty (5.1%) of the 983 participants had an intermediate allele (IA). They were similar to controls on UHDRS motor, cognitive, and functional measures, but significantly worse behaviorally on apathy and suicidal ideation. On 5 of the 9 other behavioral items and on total behavior, the IA group's scores were worse than those of controls and expanded participants, who themselves scored significantly worse than controls on 6 behavioral measures. Retention rates at 4 years were 48% for the IA group compared to 58% and 60% for the expanded and control groups.
  
  
  CONCLUSIONS
  In a cohort at risk for HD, the IA was associated with significant behavioral abnormalities but normal motor and cognition. This behavioral phenotype may represent a prodromal stage of HD, with the potential for subsequent clinical manifestations, or be part of a distinct phenotype conferred by pathology independent of the CAG expansion length.
authors.affiliation: University of Rochester, Rochester, NY, USA. Killoran:ankilloran@hsc.wvu.edu
authors.forename: Annie
authors.initials: A
authors.lastname: Killoran
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Biglan
authors.forename: Joseph
authors.initials: J
authors.lastname: Jankovic
authors.forename: Shirley
authors.initials: S
authors.lastname: Eberly
authors.forename: Elise
authors.initials: E
authors.lastname: Kayson
authors.forename: David
authors.initials: D
authors.lastname: Oakes
authors.forename: Anne B
authors.initials: AB
authors.lastname: Young
authors.forename: Ira
authors.initials: I
authors.lastname: Shoulson
mesh_terms: D000328:Adult; D000483:Alleles; D003071:Cognition / Q000502:physiology; D015331:Cohort Studies; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000145:classification / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D012306:Risk; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins