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0:00
In the third part of the talk,
I'm going to go back
to some case studies.
I'll talk a bit about cost-effectiveness
and universal screening,
and about finding
novel genes for FH.
0:17
We're starting this
by pointing out that
there are accepted
criteria for screening
developed by these
two colleagues,
Wilson and Jungner, in 1968.
The condition should be an
important health problem.
The natural history should
be well understood.
It should be detectable
at an early stage.
It should be better to treat
earlier, rather than later.
Suitable and acceptable
tests should be available.
There should be room for
test in clinical services.
The risks should be
less than the benefits,
and the costs should be balanced
against these benefits.
I'm pleased to tell you that FH
meets all of these criteria,
absolutely 100%,
and it really completely
supports the view
that we should be
screening for FH.
1:02
Let's go back to this family,
which I showed you
in the first talk.
The man had had a heart
attack at the age of 35,
and he wanted to know can
we find the genetic cause.
Can we use this information
to see if either son has FH?
The first thing to do is take
a more detailed family tree.
1:20
The pedigree I showed
you is on the left here.
Turns out that his mother had had
a heart attack at the age of 59.
Total cholesterol,
as far as we could make out,
was 7.8.
Turned out that his younger brother
had both high cholesterol, 6.7,
but also had high
triglycerides, 2.5.
And his younger sister had
high cholesterol, 8.7,
and low triglycerides.
When you look, his father
also had high cholesterol
and also high triglycerides.
This is a rather strange
pattern of lipid disorder,
and it raised the question
for us is this truly FH?
Or is it something else called
familial combined hyperlipidemia,
where you see this pattern
of both high triglycerides
and high cholesterol
in the family?
We used our DNA techniques to
screen the LDLR receptor gene.
We found a single base
pair in the LDLR gene,
which alters the proline at
position 685 to leucine.
This is a well-known
FH-causing variation
that's been well-characterised
in many individuals.
Both the original
proband, his mother,
and his sister
carried the mutation.
His father and his
brother did not.
So the question now is,
what about the four children?
You can see that the mean total
cholesterol for children is 4.9.
For FH diagnosis, it
has to be over 6.7.
You can see that at least
a couple of these boys,
they're higher than average,
but none of them are over
the FH diagnostic criteria.
You'd say they probably
don't have FH,
but the DNA test is really the way
to determine this unambiguously.
I'm pleased to say that,
using a DNA assay,
none of the children
carried the mutation.
This is very good news.
All of the four boys were
at 50% chance, each,
of carrying the mutation,
and none of them did.
So we can confirm
the parents have FH.
We can encourage
maintenance of a good diet.
And we can reassure
the boys that,
if they do maintain a
sensible, healthy lifestyle,
they're not going to be at elevated
risk of cardiovascular disease.
