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Predictive testing for Huntington disease: interpretation and significance of intermediate alleles

Authors

  • A Semaka,

    1. Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada
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  • S Creighton,

    1. Provincial Medical Genetics Programme, Children’s and Women’s Health Centre of British Columbia, Vancouver, Canada
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  • S Warby,

    1. Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada
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  • MR Hayden

    Corresponding author
    1. Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada
      Michael R Hayden, Centre for Molecular Medicine and Therapeutics, 950 West 28th Avenue, University of British Columbia, Vancouver, B.C., Canada V5Z 4H4.
      Tel: +1 604 875 3535;
      fax: +1 604 875 3819;
      e-mail: mrh@cmmt.ubc.ca
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Errata

This article is corrected by:

  1. Errata: Corrigendum Volume 71, Issue 1, 99, Article first published online: 14 December 2006

Michael R Hayden, Centre for Molecular Medicine and Therapeutics, 950 West 28th Avenue, University of British Columbia, Vancouver, B.C., Canada V5Z 4H4.
Tel: +1 604 875 3535;
fax: +1 604 875 3819;
e-mail: mrh@cmmt.ubc.ca

Abstract

Direct mutation analysis for Huntington disease (HD) became possible in 1993 with the identification of an expanded CAG trinucleotide repeat as the mutation underlying the disease. Expansion of CAG length beyond 35 repeats may be associated with the clinical presentation of HD. HD has never been seen in a person with a CAG size of <36 repeats. Intermediate alleles are defined as being below the affected CAG range but have the potential to expand to >35 CAG repeats within one generation. Thus, children of intermediate allele carriers have a low risk of developing HD. Currently, the intermediate allele range for HD is between 27 and 35 CAG repeats. In this study, we review the current knowledge on intermediate alleles for HD including the CAG repeat range, the intermediate allele frequency, and the clinical implications of an intermediate allele predictive test result. The factors influencing CAG repeat expansion, including the CAG size of the intermediate allele, the sex and age of the transmitting parent, the family history, and the HD gene sequence and haplotype, will also be reviewed.

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