What is the relationship between repetitions and onset age?
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My dad was genetic tested and he has HD. His repetition is 42. What is the probability that the repetition increases if I have the HD gene? Also I would like to know if the repetition and the onset age has a relationship and what it is for a person with a repetition of 42. My dad start showing symptoms when he was 52.
I want to get tested because I want to have kids and don’t want to pass the gene to them. But I am anxious about the results.
Karla, Young Adult, USA
A. Dear Karla,
Thank you for your email, and you raise some very interesting and important questions. I’ll try to answer each one in turn.
To answer your first question, we know that in the majority of cases when the HD gene is passed on to the next generation, the CAG repeat size stays more or less the same. Therefore, even if you have inherited the expanded copy from your dad, the most likely situation would be that your gene would also have 42 repeats (in actual fact, the exact size can be quite difficult to ascertain in the laboratory, so usually they quote an accuracy of plus/minus at least one CAG repeat). Having said that, we know that occasionally the HD expansion can be unstable when passed to the next generation, which means that it can sometimes get bigger (or smaller, although this is less common). This instability seems to happen a bit more often when the gene is passed on from a male parent.
This leads on to your second question, about the relationship between CAG repeat size and age of onset of symptoms. While it is absolutely true that CAG length shows some statistical association with age at onset, it is not the only factor involved (in fact, there is lots of research to try to identify the other genetic and non-genetic factors that could contribute to the age at which when an individual develops symptoms). This means that at the moment, CAG repeat size is of quite limited use when trying to predict when an individual with an expansion will develop symptoms. To highlight this, we know of lots of families in our clinic where different family members have developed symptoms at sometimes very different ages, despite having the same CAG repeat size.
Finally, in terms of decisions about having children / genetic testing, I think this is something a lot of people in this situation find difficult, which is very understandable. There is a lot to consider, and there is no ‘right’ or ‘wrong’ decision. What I would say is that you may find it useful to see a Genetic Counsellor, as they would be able to explore all the options with you and think about the pros and cons of each. I’m not sure which part of the USA you are living in Karla, but this website may help you to find your local Genetics service.
This HDYO article may also be helpful, as it includes more information about some of the available options around planning a family, including ‘exclusion testing’ which is a way of testing before/during a pregnancy, without revealing the status of the at-risk parent – it sounds like this option in particular would be at least worth considering if you are unsure whether or not you would want predictive testing yourself.
I hope this helps answers your questions, and please do not hesitate to get back in touch if you have any other queries.
All the best,
Last updated: May 27, 2015 13:27