I read that Huntington's is a disorder caused by dynamic mutations in the DNA, which means that a triplet sequence of DNA changes from generation to generation. Say we have the sequence ATGATGATGATG. The child of this person with have ATTATGATGATG and the grandchild will have ATTATTATGATG etc. This means that Huntington's will be worse (debut earlier) the longer the generation lasts.

My questions are: Is my understanding of dynamic mutation correct? Is there no MINIMUM age where Huntington's will debut? In other words, if a generation is very long and has Huntington's, can a baby have symptoms at birth?

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    $\begingroup$ In triplet repeat diseases it's a probabilistic addition of more repeats. 30 repeats goes to 32, or maybe to 30, or maybe less. The longer the repeat section, the more likely it is to gain or lose repeats due to duplication errors. You're not guaranteed to get just one each generation. There is likely to be a minimum age of onset where more severely affected individuals do not develop normally or die before developing chorea. $\endgroup$ – Resonating Jun 4 '15 at 15:37

At the moment, the youngest diagnosed Huntington's case was 2 years of age. This paper appears to discuss not only this boy's onset, but also the diagnosis of symptoms in the early-onset disease.

Here they research a link between age-of-onset and the length at which the repeats are.

The thing is that these repeats won't just constantly get longer. There is "slippage" during replication which causes the repeats to get longer, but it also causes the repeats to get shorter. It's possible that mom's bad chromosome may have been inherited but because of the slippage, it no longer produces Huntington's symptoms.

This image doesn't show actual mechanics of it happening, but it shows how the repeats can be added and subtracted.

From Cell

As it turns out Kayser et. al decided to look at chimps and humans to discover which of two proposed mechanisms are more likely. Their findings suggest the slippage is closest to the "heterozygote instability model".

The model suggests:

heterozygous loci might have a higher mutation rate due to mismatch repair events that occur during synapsis

To answer your question in short:

It appears that the "minimum age" so far is 2, however, that does not mean that it hasn't occurred earlier. Huntington's is characterised by a change in motor skills, and if the change occurs before birth it might not be noticed. In theory, it is possible that Huntington's symptoms can start pre-birth.


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