Some interesting reading about Huntington disease and its related gene HTT:
Huntington disease - caused by mutations in the HTT gene
The inherited mutation that causes Huntington disease is known as a CAG trinucleotide repeat expansion. This mutation increases the size of the CAG segment in the HTT gene. People with Huntington disease have 36 to more than 120 CAG repeats. People with 36 to 39 CAG repeats may or may not develop the signs and symptoms of Huntington disease, while people with 40 or more repeats almost always develop the disorder.
The expanded CAG segment leads to the production of an abnormally long version of the huntingtin protein. The elongated protein is cut into smaller, toxic fragments that bind together and accumulate in neurons, disrupting the normal functions of these cells. This process particularly affects regions of the brain that help coordinate movement and control thinking and emotions (the striatum and cerebral cortex). The dysfunction and eventual death of neurons in these areas of the brain underlie the signs and symptoms of Huntington disease.
As the altered HTT gene is passed from one generation to the next, the size of the CAG trinucleotide repeat often increases in size. A larger number of repeats is usually associated with an earlier onset of signs and symptoms. This phenomenon is called anticipation. People with the adult-onset form of Huntington disease (which appears in mid-adulthood) typically have 40 to 50 CAG repeats in the HTT gene, while people with the less common, juvenile form of the disorder (which appears in childhood or adolescence) tend to have more than 60 CAG repeats. (Does this mean if a parent has low risk of HD, their child will have a higher risk of HD?)
Individuals who have 27 to 35 CAG repeats in the HTT gene do not develop Huntington disease, but they are at risk of having children who will develop the disorder. As the gene is passed from parent to child, the size of the CAG trinucleotide repeat may lengthen into the range associated with Huntington disease (36 repeats or more).
One question is, can we use the CAG variation as a biomarker to diagnose the risk of Huntington disease?
Also, how the nucleotide repeat expansion can lead to the neurodegenetive disease?
Source: Rudnicki DD, Margolis RL, Pearson CE, Krzyzosiak WJ (2012) Diced Triplets Expose Neurons to RISC. PLoS Genet 8(2): e1002545. doi:10.1371/journal.pgen.1002545