Huntington's Disease: Relationship Between Phenotype and Genotype

Mol Neurobiol. 2017 Jan;54(1):342-348. doi: 10.1007/s12035-015-9662-8. Epub 2016 Jan 7.


Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disease with the typical manifestations of involuntary movements, psychiatric and behavior disorders, and cognitive impairment. It is caused by the dynamic mutation in CAG triplet repeat number in exon 1 of huntingtin (HTT) gene. The symptoms of HD especially the age at onset are related to the genetic characteristics, both the CAG triplet repeat and the modified factors. Here, we reviewed the recent advancement on the genotype-phenotype relationship of HD, mainly focus on the characteristics of different expanded CAG repeat number, genetic modifiers, and CCG repeat number in the 3' end of CAG triplet repeat and their effects on the phenotype. We also reviewed the special forms of HD (juvenile HD, atypical onset HD, and homozygous HD) and their phenotype-genotype correlations. The review will aid clinicians to predict the onset age and disease course of HD, give the genetic counseling, and accelerate research into the HD mechanism.

Keywords: Genotype; Huntingtin; Huntington’s disease; Phenotype.

Publication types

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

MeSH terms

  • Animals
  • Genotype*
  • Humans
  • Huntingtin Protein / genetics*
  • Huntington Disease / diagnosis
  • Huntington Disease / genetics*
  • Mutation / genetics
  • Phenotype*
  • Trinucleotide Repeat Expansion / genetics


  • Huntingtin Protein