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

Clin Genet. 2006 Oct;70(4):283-94. doi: 10.1111/j.1399-0004.2006.00668.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Age Factors
  • Alleles*
  • Child
  • Female
  • Genetic Carrier Screening
  • Haplotypes
  • Humans
  • Huntington Disease / genetics*
  • Male
  • Molecular Diagnostic Techniques / ethics
  • Mutation
  • Pedigree
  • Risk
  • Sex Factors
  • Trinucleotide Repeats