What is Huntington disease?
Huntington disease (HD) is a progressive, neurodegenerative genetic disorder characterized by involuntary movements (chorea), lack of coordination, cognitive decline, and behavioral/personality changes. The symptoms of HD are as a result of loss of neurons (nerve cells) in certain regions of the brain and usually develop in affected individuals between the ages of 30 and 50 years, although there is a form that affects children called juvenile-onset Huntington disease. The disease affects men and women alike, with a higher frequency among populations of European descent. In Western countries, an estimated 5 to 7 people per 100,000 are affected by HD. The number may actually be higher, however, because many people who have the Huntington gene do not yet have symptoms.
Huntington disease is an autosomal dominant disorder involving a defective gene on chromosome 4. That means that only one copy of that abnormal gene is needed to cause the disease in an affected person, inherited from either of that person's parents. The mutation associated with HD is an expansion of the trinucleotide repeat sequence "CAG" in the IT-15 gene (HD gene), which encodes the huntingtin protein. Although genes often have repeats as part of their sequence, when the number of repeats becomes too large, it can lead to disease. In the case of HD, instead of a normal repeat of 11 to 29 times, this section of DNA is repeated 40 to more than 80 times. This type of mutation (i.e., expansion of repeat sequences) can also be seen in a number of other genetic diseases, such as Fragile X syndrome.
In general, there is a direct 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. In addition to this, mutated alleles are genetically unstable and have a tendency to undergo further expansion as they are transmitted to future generations, increasing the disease severity in subsequent generations. This phenomenon is known as anticipation.