[Andrew Wilkie:] Apert Syndrome affects about 1 in 60,000-70,000 babies.
That means there might be about 10-12 of these children born in the UK every year.
[Anne Goriely:] What we can do, when we do genetic counselling,
is to try to explain to the parents why this has occurred
and also to try, from a research point of view,
to use these disorders and this disease as a kind of model,
to try to understand what's going on within our genome.
[Andrew Wilkie:] When we actually discovered which gene was involved:
fibroblast growth factor receptor type 2 (FGFR2),
it came as a real surprise because,
rather than being lots and lots of different changes in this gene,
there are actually just two very, very specific changes,
which cause around 99% of Apert Syndrome.
Our initial study looked at 57 families
where there was a child nearly born Apert Syndrome
and we were able to work out that, in every single one those 57 families,
the change had arisen from the father.
[Anne Goriely:] Men produce sperm on a regular basis,
every 16 days they have special stem cells which divide in order to produce the sperm.
This takes a few months, to assert the number of divisions.
Because these cells do divide on a regular basis,
they require that you copy the whole genome every time you have a cell division.
As cell divisions occur, you always have a certain chance to make errors
and this results in mutation.
Most of them are completely innocuous;
they don't encode any particular change of any interest.
But in some cases they do.
When they do this can be associated with disease
and this is essentially the process that we study.
[Andrew Wilkie:] If you look at semen,
from normal healthy semen donors,
in most of them we could measure this Apert mutation above 1 in 1,000,000.
The highest we've ever seen from the healthy man is about 1 in 6,500.
If you looked at the ages of the parents of children with Apert Syndrome,
they tended to be a bit older than the average for the population.
[Anne Goriely:] Once this mutation occurs within the spermatogonial stem cell,
these cells actually have an advantage over their neighbours,
which seems to lead to an increase in the size of the clone that they're making.
As a by-product of this effect, over the course of time,
men with this mutation produce more sperm with the mutation.
[Andrew Wilkie:] There's nothing different about a man who's the father to a child with Apert Syndrome,
it's simply a question of: which of the millions of sperm is the one that fertilises the egg?
Sometimes, just randomly, it's going to be one that carries one of these Apert mutations.
1 in 50 children are born with a fairly serious problem.
If you're a man in your 50s, studies have shown there's about an extra 1 in 200 chance
that a random child of yours is going to have some relatively serious problem.
This, and other similar pieces of work, I think were quite important
in making the authorities realise that it really wasn't sensible
to be obtaining 'healthy' sperm samples from older men.
So there's now an age limit of 40.
[Anne Goriely:] We can't say to men aged 35, "you have to stop reproducing."
Or, to men aged 17-18, "you should store your sperm."
The effect is small, it's subtle.
At an individual basis there is no particular risk,
the risk is extremely low.
However, the population level is not negligible
and so this is something which is important and we need to consider it,
not as an individual but as a society.