title: Huntington's disease: how intermediate are intermediate repeat lengths?
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).
  
  
  OBJECTIVE
  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.
authors.affiliation: Neurogenetics and Rare Diseases Centre, IRCCS Neuromed, Pozzilli, Italy. squitieri@neuromed.it
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Squitieri
authors.forename: Joseph
authors.initials: J
authors.lastname: Jankovic
mesh_terms: D000483:Alleles; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D010641:Phenotype; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins