Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2012;7(2):e29522.
doi: 10.1371/journal.pone.0029522. Epub 2012 Feb 16.

Characterization of a large group of individuals with huntington disease and their relatives enrolled in the COHORT study

Huntington Study Group COHORT Investigators  1 ; E Ray Dorsey
Collaborators, Affiliations
Clinical Trial

Characterization of a large group of individuals with huntington disease and their relatives enrolled in the COHORT study

Huntington Study Group COHORT Investigators et al. PLoS One. 2012.

Erratum in

  • PLoS One. 2012;7(8). doi: 10.1371/annotation/25881bc7-922d-4472-9efd-f0896b1a3499

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%.

Conclusion: 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.

Trial registration: Clinicaltrials.gov NCT00313495.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: J. Giuliano, D. van Kammen, and J. Warner are employed by CHDI Foundation Inc, the sponsor of this study. No other authors have financial disclosures related to this manuscript. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Enrollment and baseline classification of COHORT research participants.
Figure 2
Figure 2. Distribution of the CAG repeat length of the larger Huntingtin allele for all individuals carrying an expanded allele in the COHORT study.
See this image and copyright information in PMC

References

    1. Huntington Study Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell. 1993;72(6):971–983. - PubMed
    1. Rubinsztein DC, Leggo J, Coles R, Almgvist E, Biancalana V, et al. Phenotypic characterization of individuals with 30–40 CAG repeats in the Huntington disease (HD) gene reveals HD cases with 36 repeats and apparently normal elderly individuals with 36–39 repeats. Am J Hum Genet. 1996;59:16–22. - PMC - PubMed
    1. AMG/ASHG. ACMG/ASHG statement. Laboratory guidelines for Huntington disease genetic testing. The American College of Medical Genetics/American Society of Human Genetics Huntington Disease Genetic Testing Working Group. Am J Hum Genet. 1998;62:1243–1247. - PMC - PubMed
    1. Quarrell OW, Rigby AS, Barron L, Crow Y, Dalton A, et al. Reduced penetrance alleles for Huntington's disease: a multi-centre direct observational study. J Med Genet. 2007;44:e68. - PMC - PubMed
    1. McNeil SM, Novelletto A, Srinidhi J, Barnes G, Kornbluth I, et al. Reduced penetrance of the Huntington's disease mutation. Hum Mol Genet. 1997;6:775–779. - PubMed

Publication types

Associated data