title: Factors related to genetic testing in adults at risk for Huntington disease: the prospective Huntington at-risk observational study (PHAROS).
abstract: Huntington disease (HD) is a late onset ultimately fatal neurodegenerative disorder caused by a cytosine-adenine-guanine ( CAG) triplet repeat expansion in the Huntingtin gene which was discovered in 1993. The PHAROS study is a unique observational study of 1001 individuals at risk for HD who had not been previously tested for HD and who had no plans to do so. In this cohort, 104 (10%) individuals changed their minds and chose to be tested during the course of the study but outside of the study protocol. Baseline behavioral scores, especially apathy, were more strongly associated with later genetic testing than motor and chorea scores, particularly among subjects with expanded CAG repeat length. In the CAG expanded group, those choosing to be tested were older and had more chorea and higher scores on the behavioral section of the unified Huntington's disease rating scale at baseline than those not choosing to be tested. Following genetic testing, 56% of subjects with CAG < 37 had less depression when compared to prior to testing, but depression generally stayed the same or increased for 64% of subjects in the expanded group. This finding suggests that approaches to testing must continue to be cautious, with appropriate medical, psychological and social support.
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Quaid
authors.affiliation: Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: S W
authors.initials: SW
authors.lastname: Eberly
authors.affiliation: Department of Neurology and CHET, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: E
authors.initials: E
authors.lastname: Kayson-Rubin
authors.affiliation: Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: D
authors.initials: D
authors.lastname: Oakes
authors.affiliation: Department of Neurology and Program for Regulatory Science & Medicine (PRSM), Georgetown University, Washington, DC, USA.
authors.forename: I
authors.initials: I
authors.lastname: Shoulson
mesh_terms: D000328:Adult; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D000071058:Huntingtin Protein / Q000235:genetics*; D006816:Huntington Disease / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D019680:Trinucleotide Repeat Expansion / Q000235:genetics; D018911:Trinucleotide Repeats / Q000235:genetics
chemical_list: D000071058:Huntingtin Protein
keywords: Huntington disease; genetic testing; observational trial