Reduced penetrance alleles for Huntington's disease: a multi-centre direct observational study
Quarrell, Oliver W.J., Rigby, Alan S., Barron, L., Crow, Y., Dalton, A., Dennis, N., Fryer, A.E., Heydon, F., Kinning, E., Lashwood, A., Losekoot, M., Margerison, L., McDonnell, S., Morrison, P.J., Norman, A., Peterson, M., Raymond, F.L., Simpson, S., Thompson, E. and Warner, J. (2007) Reduced penetrance alleles for Huntington's disease: a multi-centre direct observational study. Journal of Medical Genetics, 44, (3), e68-[6pp]. (doi:10.1136/jmg.2006.045120).
Full text not available from this repository.
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.
Method: 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.
Conclusion: 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.
|Digital Object Identifier (DOI):||doi:10.1136/jmg.2006.045120|
|Keywords:||london, trinucleotide repeat, confidence intervals, disease, chromosomes, alleles, age of onset, children, england, scotland, ireland, australia, netherlands, dna, prediction, time, onset|
R Medicine > RS Pharmacy and materia medica
R Medicine > RM Therapeutics. Pharmacology
|Divisions:||University Structure - Pre August 2011 > School of Medicine > Developmental Origins of Health and Disease
University Structure - Pre August 2011 > School of Medicine > Infection, Inflammation and Repair
University Structure - Pre August 2011 > School of Medicine
University Structure - Pre August 2011 > School of Medicine > Human Genetics
|Date Deposited:||08 Sep 2008|
|Last Modified:||06 Aug 2015 02:48|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
Actions (login required)