Huntington's Scene In New Zealand
|Articles taken from the March 2003 Huntington's News. The Quarterly Newsletter of the Huntington's Disease Associations of New Zealand|
The Proverbial Crystal Ball:
Genetic Testing for Huntingtons Disease.
The Genetics of HD.
We all have 46 chromosomes in each cell, these are arranged into 23 pairs as we have two copies of each chromosome one copy from our father and the other copy from our mother.
If we are able to unravel our chromosomes we see that they are actually made up of tightly wound DNA stretches of which contain code that we refer to as genes. As we have two copies of each of our chromosomes, it follows that we also have two copies of each of our genes.
The HD gene (otherwise known as IT15) is located on the tip of chromosome 4. As we all have two copies of chromosome 4, we all have two copies of the HD gene.
This gene does not cause us any problems unless it is disrupted or stretched in an area known as the CAG repeat region. Only one copy of our HD gene needs to be disrupted to cause us a problem.
As only one copy of the gene needs to be disrupted, we say that HD has an Autosomal Dominant inheritance pattern. This means that each child of an individual that carries the fault has a 50/50 chance of also inheriting the gene fault. Both males and females can pass on the gene fault.
There is also a tendency for the onset of symptoms to get earlier in subsequent generations. This phenomenon is known as anticipation.
The area of the HD gene where the disruption occurs is known as the CAG repeat region.
¨ The general population has 27 or less repeats.
¨ Those with repeat numbers between 27 and 35 are not expected to develop HD, however there is still a risk of the gene expanding in future generations.
¨ Those with repeat numbers between 36 and 39 repeats may or may not develop the symptoms of HD, however again there is potential for the gene to expand further in future generations.
¨ When this region has stretched to 40 or more repeats the gene is disrupted and HD is expected to develop at some point in the individual life.
Diagnostic (in an individual who already has clinical symptoms)
Pre-symptomatic or Predictive (in an individual with no symptoms)
Pre-natal (in pregnancy)
These three main types of genetic testing all use the same direct testing technique with the major and most important difference being the circumstances of the individual.
These different circumstances raise very different issues in the face of testing.
Prenatal testing includes a number of options prenatal testing using the direct testing techniques is the most common form of prenatal testing used at the present time, however there are also exclusion testing and preimplantation techniques that may be utilised.
Direct testing involves looking directly at the CAG repeat region in the at-risk individual and counting how many repeats there are. The number of repeats will give an indication of whether or not the individual will develop HD (in a prenatal or predictive test) or has developed HD (in a diagnostic test).
Exclusion Testing is offered to couples where the at-risk parent does not want to know their own status.
This test does not look at the CAG
repeat region in the pregnancy, instead it aims to identify whether the pregnancy has
chromosome 4 from the affected grandparent (putting the pregnancy at 50% risk) or the unaffected grandparent (putting the pregnancy at 0% risk).
Exclusion testing requires the prenatal sample, blood samples from each of the parents, the affected grandparent and his/her partner.
Occasionally the chromosomes being tested are not sufficiently different to be able to tell them apart, therefore this test does not work for everyone. Feasibility studies are usually required prior to testing to clarify this.
Pre-implantation Diagnosis (PGD) is the newest method of pregnancy testing. In this method the egg is fertilised externally using IVF methods and allowed to grow to the 4 or 8 cell stage. At this point one cell is removed and tested using either the direct or exclusion testing methods discussed above. A cell is able to be successfully removed at this stage without causing harm to the embryo.
Due to the fact this is a new technology, PGD providers routinely recommend that it is followed up with standard prenatal testing to double check the resulting pregnancy is not at risk.
PGD is not currently available in New Zealand however is available through some Australian centres on a user-pays basis.
As with Exclusion testing, this option does not always work for everyone and feasibility studies are usually undertaken first.
Why Genetic Counselling?
The job of the Genetic Counsellor
(Genetic Associate) is not to act as a gatekeeper, or to make life more difficult. Instead the genetic associate is there to ensure
the individuals who are undergoing predictive or prenatal testing have all the necessary
information available to them so that they can make an informed choice. The genetic associate also hopes to ensure that
each individual is undergoing testing at a time that is right for them - not because their
parents, friends, partners, or children said they must have the test.
With all forms of predictive testing there are a number of issues to think about. Predictive testing as the name suggests is a way of predicting the future health of an individual. This is usually fine when it is good news, but no-one likes to hear bad news.
It is therefore important to acknowledge and think about the impact the information from predictive testing will have both on the individual undergoing testing and on the individuals family. We like to think that we have thought it all out and that the result wont affect us, but in acknowledging that we are all human it is only natural that it will have some impact.
Some of the issues discussed in genetic counselling are:
· Psychological impact of knowing about a life-threatening condition
· Psychological impact of escaping a life-threatening condition
· Possible insurance discrimination
· Possible employment discrimination
· Impact on family
· Impact on reproductive choices
Should I have the test?
Only the at-risk person considering taking the test can answer this question, no one else.
It is important to remember:
Just because the test exists, doesnt mean we have to use it!
It is natural for well meaning family members to want to arrange for their other at risk relatives to get tested too. However where proceeding with testing may be the right decision for one individual it may not necessarily be the right decision for their brother/sister/son or daughter.
An individual should pursue testing because they want to, and because the time is right for them Not because their well meaning relative or friend wants them to, or is pressuring them to.
It is OK to not want to know.
Central Regional Genetic Services.
Presented at the 2002 HD Conference,
Wellington Town Hall.
September 22nd, 2002