1. Genetic disease
1. On chromosome 4
Caused by the expansion of a CAG trinucleotide repeat encoding a polyglutamine
tract in the respective proteins. Among others, these include Huntington’s
disease and a group of spinocerebellar ataxias.
While normal-size polyglutamine exists as a random coil, when expanded it acquires
a “polar zipper” conformation with tendency towards self-interaction
and aggregation. Indeed, intracellular aggregates of the mutant protein are a
common feature of these disorders.
Polyglutamine inclusions are found in nuclei
Progression of memory and executive deficits in HD as a function of length of
the CAG triplet repeat mutation
6. Therapy with the injection of fetal or stem cells in the affected brain areas
• General outline A prototypic
mono-genic disease caused by abnormal repetition of DNA
sequences and causing a progressive motor disorder accompanied
by behavioural disturbances and cognitive impairment which
eventually develops into dementia
• Synonyms Huntington's Chorea
• Symptoms Key features of Huntington's
disease are hypotonic hyperkinesia (involuntary, exaggerated
movements of the limbs) and hyopotonic. After few years,
patients are unable to walk and to sit.
Psychiatric symptoms include delusion, hallucinations, aggressivity, impulsiveness,
personality changes, unsocial and obsessive behaviour.
Cognitive impairment is frontal type including reduced verbal fluency, impaired
executive functions and particular memory problems.
Course Early onset: 30 - 40 (within families, onset becomes
earlier every generation)
Rapid progression of motor symptoms
• Caregiver problems
• Epidemiology 5 -10 / 100.000
• Aetiology Huntington's disease
is a monogenic disease. It runs in families. There is degeneration
in subcortical nuclei, due to the toxicity induced by the
abnormal repetition of DNA sequences (triplets).
• Diagnostic procedures Reliable
genetic tests: 99 per cent precise.
• Treatment and rehabilitation Symptomatic
treatment; neuroleptics for psychiatric symptoms; safety
• Ongoing research Brain grafts,
injection of fetal brain cells into subcortical nuclei
• Available services Huntington
Disease Association in many European countries, European