Genetics of Huntington's Disease
Overview of Huntington's Disease
Huntington ’s disease (or HD) is a neurodegenitive genetic disorder, which is caused by the inheritance of a defective gene. This means that gradually over a period of time the brain and nervous system degenerate. Huntington’s disease causes the death of nerve cells in certain areas of the brain. The most damage occurs in the striatum, which then results in a loss of physical, cognitive and emotional function.
The disease can be dated back to the 16th century, but in 1872 Doctor George Huntington wrote a paper on the disease and thus it is named after him, though the original name was Huntington’s chorea. Huntington’s disease is an autosomal dominant condition, which means it is not sex linked but rather it is found on an autosomal chromosome. Specifically, the HD gene (known as IT15) is a mutation located on chromosome number 4, on the short arm near the telomere, and as a result of this it interferes with the manufacturing of the protein Huntingtin.
The actual mutation on the chromosome is known as a triplet repeat mutation. Chromosomes contain DNA sequences. In this mutation the cytosine-adenine-guanine (CAG) sequence repeats too many times. Research has shown that individuals with a CAG repeat sequence of more than 40 will develop Huntington’s disease.
The precise function of the Huntingtin protein is not known, though it is known that it plays an important role in nerve cells. It is thought that it plays a vital role in preventing cell death as well as binding proteins, transporting materials and signals around the body. Though the Huntingtin protein is found in many tissues in the body, it is most prevalent in the brain.
Because Huntington’s disease is found on chromosome number 4 and not the sex chromosomes (X and Y), it can affect both males and females, compared to a sex linked disease which can only affect one sex.
According to the Australian Huntington’s Disease Association, the estimated number of people affected by the disease is around five to seven people per 100,000. However there are locations around the world where the prevalence of HD is far greater, such as Venezuela, where the rate has been as high as 700 people per 100,000 .
Signs and Symptoms
There are three symptom groups in relation to Huntington’s disease – physical, emotional and cognitive. In the case of the physical group, symptoms commonly experienced include mild twitching of the extremities (fingers and toes). This twitching can progressively get worse and develop into chorea, which is expressed as a jerking movement in the arms and legs. Other physical symptoms can include difficulties in speech and swallowing, difficulty walking, falling easily, and a lack of coordination and tendency to knock things over.
Cognitive symptoms can include short term memory loss and difficulties making plans and an inability to concentrate at times. Emotional symptoms include depression, which around one third of Huntington’s sufferers experience, along with mood swings, apathy, and possible psychosis.
Diagnosis and Prognosis
Symptoms of Huntington’s disease do not usually appear until the individual is in their 30s or 40s. The disease is diagnosed through a series of genetic testing, a review of family history, and an assessment of physical, emotional and neurological symptoms.
Because Huntington’s disease is a dominant gene, any offspring of a carrier of the HD gene stands a fifty percent chance of inheriting and developing the disease. In order to undertake genetic testing to see if the HD gene is present in an individual, the said individual, by law, must be 18 years old and want to know their gene status before they are able to take the test to detect the presence of the HD gene. There is also prenatal testing available for parents who are carriers of the HD gene, though it is not available for children under the age of 18 mostly due to negative psychological effects on the child if they test positive for the HD gene.
There are currently no treatment options available for Huntington’s disease, as there is no current way to replace brain cells once they die. There are treatment options available for the emotional symptoms of Huntington’s disease. Anti-depressants, mood stabilisers and anti-psychotic medication are used to assist with depression, anti-social behaviour, psychosis, irritability, mania and sleep disturbances. There are also several drugs used to assist with jaw clenching and abnormal movements.
Speech and language therapy are also used to assist Huntington’s sufferers retain their ability to communicate for as long as possible. Speech therapy can also assist in overcoming the symptom of difficulties in swallowing. A high calorie diet is also recommended as sufferers burn more calories than a healthy person would due to the continuous movement they experience in their limbs. Regular exercise and specialised physical therapy can assist in keeping the muscles more flexible and stronger, and occupational therapy is used to aid memory and concentration.
Currently there is no cure for Huntington’s disease, however in the future stem cell therapy may be able to assist in treating or curing the disease. Research shows that stem cells are able to become any type of cell and therefore would theoretically be able to recreate cells which need replacing, such as the nerve cells in the brain which have died once the onset of symptoms of Huntington’s disease occurs. Due to the controversial nature of stem cell research, and the restrictions placed upon scientists in this field, it is not know if or when this technology could be used to treat diseases such as Huntington’s, or if it is actually possible to grow new brain and nervous cells in humans.
Death usually occurs within fifteen to twenty years of the onset of symptoms of Huntington’s disease. The cause of death is not from Huntington’s disease, but rather other related illnesses. Pneumonia is a common cause of death in sufferers of Huntington’s disease.
Australian Huntington’s Disease Association Inc, 2004, How Common is Huntington’s Disease, Australian Huntington’s Disease Association (NSW) Inc, viewed 26 August 2013, < http://www.ahdansw.asn.au/information/faq_prevalence.html>
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