Huntington's disease: How intermediate are intermediate repeat lengths?

Ferdinando Squitieri, Joseph Jankovic

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Huntington's disease (HD) is a devastating heredoneurodegenerative disorder associated with a wide variety of neurological and psychiatric symptoms caused by an expanded CAG repeat in the HTT gene. The expansion mutation in HTT is dominantly transmitted and codes for a protein named huntingtin (htt). Hypothesis: One hypothesis, according to a multistep mechanism, is that the intergenerational transmission of the normal repeat size causes small, progressive CAG stretch elongations in the general population from one generation to another, until a critical pathological CAG repeat threshold is reached. Mutations may originate in the offspring from paternally transmitted CAG repeats, falling within an intermediate alleles (IA) range of 27 to 35 in repeat length. Conclusions: There has been emerging evidence that some individuals with IAs might develop an HD phenotype. This presents a challenge for genetic counseling, because these individuals are often reassured that they are "disease free." However, there are many unanswered questions related to the role of IAs in the development of the HD phenotype and in the pathogenesis of HD.

Original languageEnglish
Pages (from-to)1714-1717
Number of pages4
JournalMovement Disorders
Volume27
Issue number14
DOIs
Publication statusPublished - Dec 2012

Keywords

  • CAG repeats
  • Genetic counseling
  • Huntington's disease
  • Intermediate alleles

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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