Huntington's disease is an inherited brain disorder that is caused when specific cells in the brain die. This leads to loss of cognitive function, loss of walking, eating and swallowing and eventually death. Symptoms typically start between 30-50-year old Huntington's disease is extremely rare and affects one in every 10,000 people. Huntington’s disease is caused by a mutation of the HTT gene, everyone has a copy of the HTT gene but only those with the mutation may have the possibility of getting Huntington’s disease. The mutation is an increase in a small segment of DNA called CAG. Normally, individuals have approximately 17 CAG but people who have 36 CAG repeats or more are more likely to are considered mutation-positive and will develop Huntington’s disease later in their lifetime. Huntington’s disease is often described as a family disease, children whose parents are mutation-positive have a 50 percent chance of developing the disease when they are adults as seen in diagram 1. There is no cure for Huntington’s disease but predictive genetic testing which is a simple blood test allows individuals to see whether they have the genetic mutation which causes the disease and allows people to be prepared for life in the future especially as Huntington’s disease occurs during when someone is 30-50 Prospective parents consider prenatal testing when one parent has been diagnosed with Huntington's disease or has been found to carry the gene. Prenatal testing can show whether the child will inherit the defective gene. To test the foetus, DNA is extracted from foetal cells via CVS (chorionic villi sampling) or amniocentesis which is seen in diagram 3
(CVS) is a prenatal test that is used to detect birth defects, genetic diseases, and other problems during pregnancy. During the test, a small sample of cells (called chorionic villi) is taken from the placenta where it attaches to the wall of the uterus. Chorionic villi are tiny parts of the placenta that are formed from the fertilized egg, so they have the same genes as the baby, and this allows doctors to see whether the child has the mutation in the huntingtin gene.
Amniocentesis is a prenatal test in which a small amount of amniotic fluid is removed from the sac surrounding the foetus for testing. The sample of amniotic fluid (less than one ounce) is removed through a fine needle inserted into the uterus through the abdomen, under ultrasound guidance. The fluid is then sent to a laboratory for analysis.
The genetic test for HD investigates the number of CAG triplet repeats in a huntingtin gene. The polymerase chain reaction, or PCR, is used to isolate DNA and make many copies of it. It is needed in order to make lots of copies of the huntingtin gene, allowing scientists to examine it more closely. PCR produces millions of DNA copies in a short amount of time and includes a few steps as follows. Firstly, the DNA sample is heated to nearly 100o C. DNA is normally double-stranded in a helix formation, but the heat causes the strands of DNA to separate into single strands. This process is called denaturation. Then, the sample is cooled a little. Now, primers which are a single-stranded nucleic acid utilized by living organisms in DNA synthesis can bind to each DNA strand. These are small molecules serving as the starting material for a reaction called polymerization. The goal of this reaction is to create more DNA. An enzyme called DNA polymerase makes new DNA strands by adding nucleotides, the structural unit of DNA, to the primer on each strand. It’s like adding building blocks to a pre-existing block tower. As more nucleotides are added, the strand is extended, and eventually, a new copy of the gene is made.
After creating millions of copies of the huntingtin gene using PCR, we are now ready to separate DNA fragments, in order to inspect them more closely. This can be done using a technique called gel electrophoresis which is seen in diagram 2. The principle is simple: DNA fragments are separated based on their size because smaller fragments can travel through the gel faster than larger ones. First, restriction enzymes attach themselves to DNA and cut it into small fragments. Then, the DNA pieces are placed in small wells in a gel floating horizontally in a buffer solution. This solution is located between two electrodes, one positive and the other negative. Once an electric current is passed through the gel, the fragments of DNA begin to move. DNA is negatively charged, so it is attracted to the positive electrode. The smaller fragments move faster than the larger ones, so they move across a greater distance towards the positive electrode.
Now that the fragments of DNA have been separated, the technicians are ready to inspect each DNA fragment. They do this to evaluate the number of CAG repeats in the huntingtin gene. Individuals who do not have HD usually have 28 or fewer repeats. Individuals with HD usually have 40 or more repeats.
Researchers from University College London (UCL) and University College London Hospitals (UCLH) have devised a simple blood test that can identify early physiological changes caused by Huntington’s disease. The test locates the two biomarkers, the neurofilament light protein associated with nerve damage and the disease-causing mutant huntingtin (mHTT) protein One of the most challenging issues for all HD symptomatic and at-risk persons is the profound denial of the presence of HD in the family and discrimination and shunning of the affected individuals from their own family and from the society. People with Huntington's disease may also be refused life insurance and other forms of insurance, this means that families financially may be in poorer position as the person affected Huntington's disease will not be covered by any form of insurance. These tests may also emotionally affect parents if they’re child has the mutation as they believe they have harmed their child.
However, these tests allow families to be proactive in preparing for the future and can offer peace of mind for those who parents had Huntington’s disease, but they themselves don’t. These tests also enable those with the mutation to begin gene therapy which has a higher success rate if started sooner.
Individuals in a survey conducted were overwhelmingly in support for the individual to have the decision to have genetic testing even if they were a child as it was the child’s life. On the other hand, in the survey those that opposed allowing the child the choice said that as they would not be able to understand the consequences of their choice, so an adult should make help them make that decision.
In another question in the survey “is it ethical to manage a disease which an individual is susceptible to if they aren’t aware that they are susceptible” Responses were fairly balanced out some were of the view that if a person does not know and are happy, testing which could remove the happiness should not be attempted, others were of the opinion that testing should be conducted so that the individual would have a greater chance of survival as the chance of gene therapy being successful depends on the time it is started.