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Huntington’s disease (HD) or chorea is a progressive, neurodegenerative genetic disorder characterised by chorea (involuntary movements), in-coordination, cognitive decline and behavioural/personality changes. In general, develop in adults between the ages of 30-50 years, although a small proportion (≈5%) show before the age of 20 years. This is referred to as Juvenile-onset Huntington’s disease. The symptoms of HD are as a result of loss of neurons (brain cells) in certain regions of the brain.
Huntington’s disease is an disorder. The mutation associated with HD is an expansion of the trinucleotide repeat sequence, CAG, in the IT-15 (HD gene) which encodes the huntingtin . Although genes often have repeats as part of their sequence, when the number of repeats becomes too large, it can lead to disease. The result of this expansion is defects or deficiencies in the huntingtin protein leading to disease. This type of mutation (i.e. ) can also be seen in a number of other genetic diseases such as .
Four classes of HD have been described:
- The normal allele containing ≤ 26 CAG repeats (less than or equal to 26 CAG repeats).*
- Alleles containing between 27-35 CAG repeats. Individuals with these alleles will not develop HD but there is the potential to expand into the disease range in the next generation.
- Intermediate alleles containing between 36-39 repeats.*
Individuals with these alleles may or may not develop symptoms of HD.
These alleles are described as having reduced or incomplete penetrance.
- The HD allele containing ≥ 40 CAG repeats (greater than or equal to 40 CAG repeats).*
All individuals with these HD alleles will eventually develop symptoms of HD, i.e. having high or full penetrance.
* Note that these numbers may vary slightly between different laboratories and regions.
In general, there is an inverse relationship between the number of repeats and the severity of disease, that is, the larger the repeat size, the more severe the symptoms and the earlier the onset of disease. However, the repeat size cannot be used to indicate the age of onset. In addition to this, mutated alleles are genetically unstable and have a tendency to undergo further expansion more commonly through paternal transmission to future generations, increasing the disease severity in subsequent generations. This phenomenon is known as anticipation.
Huntington’s disease tends to have a higher frequency in populations of European decent and in Australia affects between 6-7 people in every 100,000. HD remains prevalent in the population because of its relatively late onset, i.e. affected individuals are usually during their reproductive years, allowing the mutation to be silently passed onto subsequent generations.
For further explanation on patterns of inheritance see Genetic testing
Last Review Date: April 27, 2023
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