[tri-med] Re: question regarding genetic tests: Cells counted etc
- From: "Karen" <karens@xxxxxxxxxxxxxxxx>
- To: <tri-med@xxxxxxxxxxxxx>
- Date: Fri, 13 Feb 2009 09:24:19 +1100
----- Original Message -----
From: "Barbara
> I was looking at the genetic testing results and they state the following:
> I was thinking that these numbers seem to be very small. Does anyone know
> how many cells were involved with their own child's testing?
If you are thinking of standards there really are none. Each lab determines
their own. A test can consist of one cell or 100 or 600 - it depends on the
test and the circumstances and most importantly the protocol of the lab.
Bottom line with g-banding (550 resolution) there is no minimum - 1 cell is
looked at with pre-implantation because thats all that they get.
5 is generally considered the bare minimum for an amnio or peripheral
lymphocyte (blood) culture but 20 is better science and what most labs now
consider the minimum. 100+ is what I consider (and most "good" labs
consider) the bare minimum if you are wanting to rule out mosaicism,
artefact and human error. In reality a lab tests what they get and what they
have the time to test.
If a lab tests 100 cells and only 1 shows a trisomy - then they normally
wont report it. The minimum percentage a lab accepts is 5% of the cells
tested. Thats normally because every lab differs and it probably depends on
how litigation minded they are. One lab here where I am reports all, another
reports only those greater than 5%.
But as always there are qualifiers. Trisomic cells don't always culture well
meaning that they either don't grow or grow slowly so its not always easy to
get a lot of cells especially in a short space of time.
If you are considering that mosaicism may be a possibility then a FISH is
the better test because it tests many cells rapidly BUT it doesn't actually
look at individual cells it only looks at signals and that signal may come
from "part" of an extra chromosome or a whole they don't know unless they do
a g-banding. Also the lab person only has a few minutes to count the
signals, some may fade quickly, be hidden behind others etc. And most
importantly it only looks at the chromosome its testing for so for example
if they test for 18 it wont show up a problem with 17. Thats why g-banding
is the definitive genetic test and why I have reservations about rapid FISH
testing for a prenatal diagnosis. A rapid FISH usually only tests
chromosomes 13, 18, 21 and X that is the "common" trisomies.
Then we go into grades. Most people don't even realise that there are grades
of testing. Very simply a grade 1 means that they looked at the cells of one
culture. Grade 2 - 2 different petrie dishes (called flasks) Grade 3 - three
and Grade 4 four different cultures. And thats because if they only do one
culture its possible that the problem simply occured in the culture. That is
the original cells taken were fine but divided incorrectly in the petrie
dish. Less likely to happen if you do more than 1 culture.
G - Banding (550 resolution) is the definitive test. Manually done by a lab
person and the most time consuming. Takes at least 3 days but usually a week
or more depending on how well the cells grow and of course how quick off the
mark the lab is. Most labs do "batches" and you may have to wait for the
next batch. Despite being the definitive test (meaning the only test on
which a diagnosis can be based) it is not the best test for picking up
mosaicism. Thats because its a numbers game. If you have 10% of the cells
with a trisomy and you only test 10 cells then you may miss it because only
one will show the trisomy. If you test 100 cells then your more likely to
pick up a few of the trisomic cells.
And thats why labs don't usually give percentages instead they give numbers
and grades. Its doctors that convert to percentages which mean nothing
because it depends on where the cells are and what effect they have had not
how many. Thats why a child with 10% trisomic cells in blood has as much
possibility of dying as a child with 100% - it depends on what problems that
the trisomy caused not the trisomy itself. Trisomy itself is not a disease
and it does not cause death - its a condition that MAY lead to problems that
may cause life threatening conditions.
Usually they test amniotic fluid or blood. An amnio tests the placental
cells (which may have a trisomy and yet the baby may not) and sloughed off
skin cells. It does not test blood or the babies internal cells until about
22 weeks when the baby starts swallowing and weeing amniotic fluid. What
shows up in blood may be very different to other organ systems eg skin,
heart, urinary etc. Thats why an amnio MUST be confirmed after birth in my
opinion (and thats why they normally do a blood test after birth)
So they never really test for mosaicism because to do so they would need to
test several organ systems - they are looking for signs of mosaicism. If the
trisomy appears obvious many doctors and labs don't go looking for mosaicism
because they are only looking for hope for the parents mind. Mosaicism is
usually only looked for if its suspected because the baby doesn't appear to
be "sick" enough has lived longer than expected or does well
developmentally.
In reality we ALL have some trisomic cells in our body at any given time and
if we look hard enough then we will find them. Similarly any child with a
trisomy will also have some "typical" cells if we look hard enough.
As for your question - Alex has had numerous genetic tests and they have
done everywhere from 1 cell (thats all that they could get and that was from
urinary casts and if you go on that percentage he has 100% trisomic cells)
to 600. With his first test they did 15 and missed the trisomy totally (even
though his blood has since never showed less than 70% affected cells so it
raises the question of whether it really was his blood and we will never
know because the original slide has been conveniently "lost" so I cant get a
DNA test done). They have also FISH'ed 600 skin cells and missed the trisomy
yet the next time that they tested they only FISH'ed 300 skin cells and
found 33% showed the trisomy.
Are genetic tests reliable - statistically they say they are 98% reliable
but I have since discovered that because labs self regulate that may not be
accurate which is definitely my personal experience. There are way tooooooo
many variables.
Life consists not in holding good cards but in playing those you hold well.
-- Josh Billings
Keep Looking For Rainbows!!
_--_|\
/Karen \
\ _.--._ /
v Karen, Mum to Alex (14 years, T-18 Mosaic)
http://members.optushome.com.au/karens
Building ___ooOOoo__ Rainbows
www.trisomyonline.org
Families Helping Families On-line
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