title: Reduced penetrance alleles for Huntington's disease: a multi-centre direct observational study.
abstract: OBJECTIVE
  To obtain penetrance data for Huntington's disease when DNA results are in the range of 36-39 CAG repeats and assess the consistency of reporting the upper allele from two reference centres.
  
  
  METHODS
  Data were collected anonymously on age of onset or age last known to be unaffected from a cohort of individuals with results in this range. DNA samples were re-analysed in two reference centres. Kaplan-Meier analysis was used to construct an age of onset curve and penetrance figures.
  
  
  RESULTS
  Clinical data and concordant DNA results from both reference centres were available for 176 samples; penetrance figures (and 95% confidence intervals) for this cohort, at age 65 and 75 years, were 63.9% (55.5% to 73.2%) and 74.2% (64.2% to 84.2%), respectively. Inclusion of 28 additional subjects for whom repeat DNA results were unavailable, obtained from only one reference centre, or discrepant by one repeat within this range, gave penetrance data (including 95% confidence intervals) at ages 65 and 75 years of 62.4% (54.4% to 70.4%) and 72.7.% (63.3% to 82.1%), respectively. 238 duplicate results were available from the reference centres; 10 (4.2%) differed by one CAG repeat in the reporting of the upper allele and in two (0.84%) of these cases the discrepancy was between 39 and 40 repeats.
  
  
  CONCLUSIONS
  When DNA results are in this range, a conservative approach is to say that there is at least a 40% chance the person will be asymptomatic at age 65 years and at least a 30% chance the person will be asymptomatic at age 75 years.
authors.forename: Oliver W J
authors.initials: OW
authors.lastname: Quarrell
authors.forename: Alan S
authors.initials: AS
authors.lastname: Rigby
authors.forename: L
authors.initials: L
authors.lastname: Barron
authors.forename: Y
authors.initials: Y
authors.lastname: Crow
authors.forename: A
authors.initials: A
authors.lastname: Dalton
authors.forename: N
authors.initials: N
authors.lastname: Dennis
authors.forename: A E
authors.initials: AE
authors.lastname: Fryer
authors.forename: F
authors.initials: F
authors.lastname: Heydon
authors.forename: E
authors.initials: E
authors.lastname: Kinning
authors.forename: A
authors.initials: A
authors.lastname: Lashwood
authors.forename: M
authors.initials: M
authors.lastname: Losekoot
authors.forename: L
authors.initials: L
authors.lastname: Margerison
authors.forename: S
authors.initials: S
authors.lastname: McDonnell
authors.forename: P J
authors.initials: PJ
authors.lastname: Morrison
authors.forename: A
authors.initials: A
authors.lastname: Norman
authors.forename: M
authors.initials: M
authors.lastname: Peterson
authors.forename: F L
authors.initials: FL
authors.lastname: Raymond
authors.forename: S
authors.initials: S
authors.lastname: Simpson
authors.forename: E
authors.initials: E
authors.lastname: Thompson
authors.forename: J
authors.initials: J
authors.lastname: Warner
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015331:Cohort Studies; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000453:epidemiology / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D019683:Penetrance; D015203:Reproducibility of Results; D019680:Trinucleotide Repeat Expansion