February 3, 2025 • 36 mins
This episode features a conversation with genetic counsellor Sarah Long, who shares her insights into non-invasive prenatal testing (NIPT) and its implications for expectant parents. We discuss the importance of positive predictive values, variations of unknown significance, and the ethical dilemmas faced by families navigating genetic testing. • Exploring the evolution and methodologies of NIPT • Clarifying the concept of positive predictive value in genetic testing • Highlighting the crucial role of pre-test and post-test counselling • Discussing the emotional impact of variants of unknown significance • Understanding parental perspectives on knowledge versus uncertainty in testing • Addressing the misinformation surrounding the MTHFR gene • Reflecting on the ethical considerations of genetic screening and disability Listen to the episode for an enriching exploration of genetics that concerns us all!
Demystifying Genetics is sponsored by TrakGene https://www.trakgene.com/
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Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Matt Burgess (00:01):
Hello and welcome to Demystifying Genetics podcast
.
My name is Matt Burgess and Iam your host.
I am a genetic counsellorliving and working in Melbourne,
australia.
In this episode, which isepisode one of season four, I
speak with genetic counsellorSarah Long in Perth, western
(00:21):
Australia.
Join us for an interesting chatabout her research and clinical
genetic counselling dilemmas.
Hello, sarah.
Sarah Long (00:32):
Thanks so much for having me.
Matt Burgess (00:34):
Welcome to Demystifying Genetics.
It is episode one of seasonfour.
I'm really excited.
Sarah Long (00:41):
Yeah, I've actually spent the afternoon listening to
some past episodes, so I had abit of an idea what to expect oh
good, and I can see that you'resitting in the sun at the
moment.
You're outside and enjoying thethe sunshine yep, I'm based in
Perth in Western Australia andit's about 25 degrees, so it's
absolutely perfect oh beautiful.
Matt Burgess (01:02):
I'm inside in my study and I've got my beautiful
dog Banjo next to me and I justhope that he doesn't see the cat
next door and start barking.
Sarah Long (01:10):
Well, I've got Loki, who's my puppy, out here and
before he decided to scare offanother dog so he was going
absolutely off.
So hopefully he doesn't arc upeither.
Matt Burgess (01:22):
Well, it's a very dog-friendly podcast, so that is
fine.
I'm really excited about ourconversation today.
I would like to talk to youabout all things reproductive
genetic counselling and Iunderstand that is the topic of
your PhD.
Sarah Long (01:39):
Yeah, so my PhD is about non-invasive prenatal
testing using platforms likeholoxone sequencing to look for
hundreds or thousands of geneticconditions in pregnancy, and
that basically started when Istarted, when I was working in
prenatal for the public hospital, and it was.
Nipt was quite new, but italready evolved into doing
(02:03):
things like microarrays and withthat became a lot of
controversies with positivepredictive values and problems
like that, because the PPVs weremuch lower for micro deletions
and micro duplications and itstarted getting me thinking well
, what happens when we combineit with other technologies and
we can start testing for singlegene disorders on a population
(02:25):
level?
What will happen then?
And that's really where the umimpetuous for doing a phd came
from.
It was a hypothetical uh-huhokay.
Matt Burgess (02:35):
So for the non-genetic counselors listening
to this podcast, I think I'mgoing to break down what you've
just said.
So I think maybe just startwith okay, we talk about NIPT.
I know at work sometimes Irefer to it as NIPS or NIPS.
Could you sort of justbasically explain what this test
(02:55):
is and how it's used?
Sarah Long (02:59):
Absolutely so.
It's a screening test.
It's not a diagnostic test,which is really important to say
and basically it takescell-free fetal DNA, so DNA from
the fetus that's floatingaround in the mother's blood,
and it compares the maternal,the mother's DNA to the fetus's
DNA to see whether there's anyextra or missing bits so you can
(03:21):
tell whether a baby might havetriathlete 21 or Down syndrome.
But you can also look forsmaller parts of the chromosomes
that might be missing orduplicated that can cause
problems like Angelman syndromeor Carter-Willie syndrome, and
you can do that across the wholegenome now.
So you can look forduplications and deletions
across the whole genome.
And in the last couple of yearsa big company has actually
(03:44):
released a test that now looksfor single gene disorders.
The last time I checked therewere 25 single gene disorders on
this list that you could bescreened for in pregnancy.
So my hypothetical of having atest that could screen hundreds
or thousands of geneticdisorders really isn't that far
away commercially.
Matt Burgess (04:04):
Yeah, yeah, I know , I just spent a few years in
the United States and I workedfor a company over there that
had a single gene NIPT test.
So, yeah, very interesting.
And I guess the other thingthat I sort of just maybe we can
define before we move on ispositive predictive value or PPV
(04:26):
.
Yeah, what does that mean to alayperson?
Sarah Long (04:31):
Yeah.
So one of the big problems whenNIPT first came out was it was
advertised as 99% sensitivityand a lot of people doctors and
patients took this to mean 99accurate.
Now a screening test.
You don't use accuracy becauseit's not a diagnostic test.
(04:51):
It's not saying if we say thisperson has down syndrome, 99 the
time it's correct.
What it's saying is that ifthere's a population of 100
people and they all have ascreening test positive for Down
syndrome, then 99% will bedetected and one won't be
(05:11):
detected.
And the other side of that isspecificity.
Sorry for stumbling over that.
And that's saying if we have100 people who have a baby with
Down syndrome, how many will bepicked up?
And we know that specificity isreally good for NIPT.
It's over 90% but it's not 100%.
(05:33):
So it doesn't detect allpregnancies with trisomy 21.
And I'm using trisomy 21 orDown syndrome as the example
because that's the conditionthat has the highest sensitivity
and specificity.
When you start looking at microduplications and dilations, it
drops quite low and when youlook at things like the sex
chromosomes, it drops quite lowagain.
Matt Burgess (05:54):
Um, some of the sex chromosomes has have a
positive predictive value of the50 kind of thing yeah, when I'm
speaking to women and couplesabout this test or this screen,
um, like I, I think of myselfand I think you know I am a
genetic counselor and part ofour role is to to give people
(06:18):
information and to explain it,and obviously we know much more
about the test and part of ourrole is to just give as much
information as the patients needin order to make their decision
.
But, on the other hand, I kindof think sometimes, like when it
comes to my own sort ofpersonal medical information,
like I don't know, likeignorance is bliss or you know,
(06:39):
like I am very happy for thedoctors and medical staff to be
quite paternalistic and say,like Matt, do this or don't
worry about this.
And I really struggle because Ithink it's completely
understandable when someonecomes in and says how accurate
is this test, and we kind ofknow what they mean.
(07:01):
But it is actually quitedifficult to kind of really
break down Like you don't wantto give somebody a statistics
lesson and you know, I don'tknow, is that something that you
kind of have got a better with?
That sort of explaining?
Like if I said, oh, howaccurate is this test in a
clinic, how do you sort ofexplain that?
Sarah Long (07:27):
this test in a clinic?
What?
How do you sort of explain that?
So the interesting thing is Idon't work clinically in
prenatal.
I work clinically two days aweek in familiar cancer and I
work three days a week in aresearch position doing prenatal
.
And even if I did workclinically prenatal at the
public hospital I work at, wedon't see people before their
NIPT tests.
We only see them after they'vehad a diagnosis confirmed on
(07:49):
amnio and then we do thecounselling because of the sheer
volume of NIPT that's beingdone in the general population.
So I think that there is a lotof misinformation about how NIPT
works, because I don't thinkthat a lot of general doctors
understand the difference inbetween a screening and a
diagnostic test, although Ithink it has gotten better.
(08:10):
When NIPT first came in inWestern Australia we had
patients who were ending theirpregnancy based on the NIPT
results before havingconfirmation with amnio, and we
quickly communicated to doctorswhy that was inappropriate.
So it's not something I have todo on a clinical basis very
often, um, it's something that Ido as part of my phd and it's
(08:34):
something that I've been doing.
Um, when I talk to patients inmy research role, they often
bring up their niptT results andask questions about them.
Matt Burgess (08:50):
Yeah, I think that's difficult in research
when you're sort of interviewingpeople and then they have like
a clinical question.
It's like, oh, you know, there'sa bit of a fine line there with
sort of being able to answerthe question.
But I think you bring up areally interesting point about
pre-test counselling andpost-test counselling and
post-test counselling.
And you know, in geneticcounselling it wasn't that long
ago and I mean, there's probablystill people out there that do
(09:13):
that, that do this, where theyspend an hour with a patient
talking about the pros and consof testing one particular gene,
and it's kind of like those daysare gone now.
I think you know like, um, itwasn't that long ago that we
were sort of the gatekeepers ofgenetic testing and like all
(09:36):
genetic testing went throughgenetics and, um, now it's kind
of like every specialty isordering genetic testing and a
lot of people aren't gettingthat pre-test counselling.
And is there a way that you andlike the genetic counsellors
you work with can seefacilitating that?
(09:58):
Like, you know, not everyonecan sit down, but, you know, can
we record a video?
Or, you know, can we get peopleto have a fact sheet?
Or, you know, can we empowerthe general practitioners to
sort of give more informationbefore the test yeah, well,
there's been a few things.
Sarah Long (10:15):
So we've had mainstreaming come in for
ovarian cancer testing inwestern australia.
Um, it's coming for cancertesting, but the doctors and the
surgeons, the oncologists, havebeen a bit more reluctant,
because I think at the startthey were quite keen.
They thought, oh, instead ofwaiting for a few months to get
a test result, I can just orderit and be done.
And then the first lot ofbooths came back and they all
(10:38):
panicked and went why are wedoing this?
We don't know what this means,send it to genetics.
And then, of course, they startdealing with the ethical issues
involved and I think they'vereally backed off and they're
sending way more to us becauseit was, I think they realised
that it's a lot more complex andthey don't have the time to do
a lot of the counselling.
But what we've done is done alot of education, done a lot of
(11:04):
talking at multidisciplinarymeetings about how to facilitate
testing and what are some ofthe issues involved.
We also developed a consentsheet and the consent ticks off
a lot of the issues that shouldbe discussed in pre-test
counselling.
So if they go through theconsent properly, they should
have had the basic issuescovered, if that makes sense.
So, yeah, that's really helped.
(11:28):
I think in some cases thepre-test counselling isn't as
important as in others.
So what I mean by this is, witha lot of the ovarian cancer
patients, they're usually a lotolder, so we're talking women in
their 80s or 90s.
For a lot of them, they'vealready had their children.
They might not have a lotlonger to live, so it's not
(11:51):
about other cancers that mightpop up in future.
A lot of these are quite latestage cancer patients and the
main reason they're having thetesting is for treatment
purposes, so they can take PARPinhibitors for their ovarian
cancer if they're BRCA1 or BRCA2positive.
So I think that's reallydifferent for when you're seeing
a 40-year-old for breast cancerwho's got two young children
(12:15):
and brothers and sisters andthey're worried about the impact
on their family and what it'sgoing to mean for them.
So I think it's the context aswell as to whether mainstreaming
is appropriate or not in thosecircumstances.
Matt Burgess (12:31):
Yeah, and I think that makes sense.
But what I really like or whatI take away from that is the
value of genetic counsellors.
On one hand, I think evenworking in like a big public
hospital, you know, with a largeclinical genetics department,
(12:51):
there is still a lot of workersthat do not know what a genetic
counsellor is or what we do.
Or you know sort of what ourtraining is, genetic counsellor
is or what we do, or you knowsort of what our training is.
But when the doctors out therekind of requested that they be
able to order their own genetictests and then we helped
facilitate that through likethis mainstreaming sort of
concept, and then all of asudden they were like, oh,
(13:14):
actually this is a bit harderthan what I was expecting.
It's sort of I don't know ifheartwarming is the right word,
but you know like it'sencouraging to hear that they
value genetic counselling andthey can see that we can
actually help in the process andthe management of their
patients.
Sarah Long (13:32):
Absolutely and I think that's really come out.
They do value us.
We've had we started attendingMOLS years ago and they've
started up a few more meetingsaround Perth.
I'm involved in the breastcancer ones and the latest time
they started one up theyspecifically requested a genetic
counsellor join them.
So they are recognising ourvalue in multidisciplinary
(13:55):
management of patients withcancer.
We've also got renal andcardiac genetic counsellor
specialties working at thepublic hospital now and they
work very closely withcardiologists and renal
specialists.
So we are expanding into otherareas where these specialists
are saying we need geneticsinput, we need a genetic
counsellor on board.
Matt Burgess (14:14):
Yeah, and I guess you know when you order a
genetic test, I think you knowthe layperson would be familiar
with the test either coming backpositive or negative.
But you mentioned the word VOOSand just to sort of explain
that that means a variant ofunknown significance.
So sometimes when we do genetictesting the lab may find a
(14:37):
change in the gene and weliterally do not know what it
means, or there's not enoughevidence to say that that is
actually disease causing or not.
And yeah, it's been myexperience as well that some of
the doctors you know, as soon asa variant of unknown
significance comes up, they'relike oh, I don't know how to
(14:58):
manage this.
Sarah Long (14:58):
Like, oh, let's sort of handball it back to genetics
absolutely, and I think vocesor variants of unknown
significance are definitely thebane of genetic counselors
existence.
Um, it's hard to communicate topatients.
It's hard to communicate topatients family, who might just
hear there's something found ina gene and then they contact us
wanting testing.
And even doctors sometimes makeclinical decisions based on
(15:24):
VUSAs and we've had to go backand tell them that's really
inappropriate.
This is not a clinicallyactionable gene change.
But yeah, there's definitelybeen antidotal cases of people
having prophylactic surgerybecause of VUSA and stuff like
that.
Matt Burgess (15:39):
Okay.
So I'm a bit surprised that wewent into cancer.
I didn't think that we would betalking about that today.
Sarah Long (15:47):
Yeah, so my PhD is actually mixed methods.
It's qualitative andquantitative.
We started out by deciding toget some basic ground-level
knowledge about women andgenetic conditions, and lots of
conditions, whether people withchildren with genetic conditions
would have wanted to know.
(16:07):
So we did.
I did, uh interviews with 30women 10 who self-identified as
healthy with no children, 10 whoself-identified as healthy with
healthy children and 10 whoidentified as healthy with
children with a de novo geneticcondition that wouldn't have
been picked up in pregnancyusing the technologies available
(16:27):
at the time of the interview.
Matt Burgess (16:31):
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But going back to sort ofreproductive and sort of what
(17:17):
your research has been in ofreproductive and sort of what
your research has been in, youknow I kind of consider myself a
qualitative researcher and sortof one of my favourite
approaches is using aphenomenological approach.
I always have to be carefulsaying that big word and I think
that that's sort of yourapproach as well.
(17:40):
Can you tell us a little bitmore about sort of the different
studies that you've done usingqualitative research?
Sarah Long (17:49):
Neither parents are carried.
It happens in the egg or thesperm before conception and then
when they join up together, thechild has a genetic condition
that neither parent's thecarrier's on.
So even if the parents hadundergone carrier screening
before conception, this is notsomething they could have
prevented in any way.
And what did you find?
We found a lot of things.
(18:10):
We published quite a few paperson the qualitative data.
There was actually quite goodgenetic literacy among all the
cohorts, although the cohortswith women with genetic
conditions had a lot moreknowledge about genetic
conditions in general because ofexposure to support groups.
And even the women withoutchildren, who tended to be a bit
(18:31):
younger, had quite a lot ofknowledge about genetic
conditions, and some of it wasfrom the media.
So one person had seen grey'sanatomy and said oh you know, I
saw this genetic condition, I'mdefinitely going to get tested
for it.
And another person had seensomething in the newspaper about
a couple with a child with craba disease and she was adamant
(18:53):
she was going to get tested forcrab a disease because it was a
really heartbreaking story.
So that was quite interestingto hear the exposure people had
to different genetic conditions.
It was really interesting thatnot a lot of people knew what
they had been screened for ifthey did have children.
So a lot of them said, oh, Ihad screening for Down syndrome,
but they weren't really awarethat there were other things
(19:17):
screened for and they weren'taware that you could get other
things screened for, and theyweren't aware that you could get
other things screened for,especially before pregnancy as
well.
Um, probably the mostinteresting paper is would I
have wanted to know, which isabout the experiences of the
mums that had children with denovo genetic conditions, and I
(19:37):
asked them would you have wantedto know about your child's
genetic condition while you werepregnant?
And about half of them said yes, I would have wanted to know,
because this is a really hardlife and I probably would have
ended the pregnancy.
So that was quite brutallyhonest.
And half of them said no, Iwouldn't have wanted to know,
because I probably would haveended the pregnancy and they've
brought so much joy and richnessinto my life.
(19:59):
I couldn't imagine my lifewithout them here.
So it was a really interestingperspective and one that raises
the ethical issue of if we dostart screening for more
conditions.
Are we stigmatising people withdisability and are we doing
them a disservice by enablingpeople to end these pregnancies.
That might be individuals wholead really rich, fulfilling,
(20:23):
joyful lives despite the factthey have genetic conditions.
And on the flip side to that is, I believe every child should
be a wanted child, no matterwhat the circumstances.
And if a parent feels theycan't parent a child with a
severe genetic condition, thenwho am I to say you shouldn't.
You know, this child might havea great life.
(20:44):
You should parent this child.
So it's.
It's one of those conundrumsthat has come up in my PhD that
I've I've written about and Itry to acknowledge in all my
discussions, but I don't thinkthere's an easy answer question,
but I don't think there's aneasy answer.
Matt Burgess (21:05):
Wow, there's so much there.
Yes, I, and one of the thingsthat we sort of touched on
before was that you know thesenewer sort of versions of the
non-invasive prenatal screen.
Um is looking at conditionslike micro deletions or sort of
uh rarer changes that can occurin our genome and that the
positive predictive value isn'tthe highest for this um.
(21:29):
So I guess practically whatthat means is um women could
have these tests.
It comes back increased riskand then um, it's actually not
the case in the child.
You test the child.
Um test the fetus and the.
They do not have the conditionthat um was brought up on on the
(21:52):
test.
What did women?
Did women sort of talk to youabout their feelings, about, you
know, conditions being included, whether sensitivity wasn't
that high?
Sarah Long (22:04):
So at the time that I did the test, none of the
women sorry the interviews noneof the women were pregnant and
had NIPT.
Most of the women had firsttrimester screening because it
was still when NIPT was quitenew.
So we asked about what theythought about NIPT.
In the quantitative study,which was the larger online
(22:25):
study that we generated thequestions from themes identified
in the qualitative study, but Ididn't ask directly about what
they felt about NIPT.
Having said that, a few yearsago a friend reached out and
said I've just had this Harmonybook.
I don't know whether I canreached out and said I've just
had this harmony I don't knowwhether I can say the name,
sorry, I just had this NIPT testand it's come back saying the
(22:45):
baby has 22q11 syndrome.
What do I do Now?
Every genetic counsellor knowsthat you don't counsel your
friends.
So I immediately found thewebsite and hooked her up with
the genetic counsellor.
But I did tell her look, look,the positive predictive value is
low.
So this is something that it's.
It's not a.
(23:06):
You know it's.
It's not a hundred percent,it's not a diagnosis.
Talk to the genetic counsellorand then you can arrange an
amniocentesis if you want.
And um, she talked to thegenetic counsellor associated
with the company and she had areally good experience with them
, which was great.
I think they told her thepositive predictive value was
(23:26):
around 40%, so that really puther mind at ease.
And then I actually went withher to the amniocentesis because
her partner had to look aftertheir other children look after
their other children.
So I was there to hold her handand watch my 800th amnio go
through.
(23:47):
It's a bit different when it'syour friend on the table, though
I was much more nervous than Iusually am and the baby looked
fine.
An ultrasound, no cardiacdefect or anything, and the baby
came back completely fine andhe's actually my godson now.
So that, yeah, yeah.
So so that was lovely.
Um, it was a good.
It was a good outcome, but itwas horrific for my friend who
(24:10):
already had two kids and youknow a 22q11 is so variable and
you can be absolutely fine oryou can have quite a lot of
delay and you just don't get anidea of what would this look
like for me and my family.
So while I haven't had toclinically counsel about it, I
have a quite personal experiencewith it yeah, it is very
(24:36):
difficult.
Matt Burgess (24:37):
I feel like sometimes we can sort of give
the diagnosis and the people youknow, people say what does that
mean?
And that's a really hardquestion to answer zone around
(25:04):
the moment where it just seemsamazing that they're going back
to a law, um from the 1800s,about termination and, um, you
know, having lived in americaand kind of seeing um the
medical system over there andhow complicated it is and how
expensive it is, and then comingback to australia, um, I'm just
wondering about termination andhow easy is it for women to
(25:24):
access termination, relativelyspeaking, in Australia?
Is that something that you cansort of comment on or do you
have sort of thoughts about that?
Sarah Long (25:35):
Yeah, yeah.
So in a paper I'm writing upfor my research.
I don't remember off the top ofmy head I'm writing up for my
research.
I don't remember off the top ofmy head, but basically a lot of
the states require two doctorsafter a certain gestation to
sign off on it.
Wa had some of the mostrestrictive laws where after 20
weeks you'd have to go to aministerial panel of experts who
(25:56):
would say this condition issevere enough so that allow late
termination.
Thankfully our abortion lawshave changed in WA.
You can now go to 24 weeks andhave late termination.
Thankfully our abortion lawshave changed in wa.
You can now go to 24 weeks andhave a termination.
And the reason that this is soimportant is because most fetal
anomalies get picked up at the20-week scan.
So if the limit to abortion is20 weeks in in a state, then
(26:19):
you've got very little or almostno time to make a decision
before that decision is out ofyour hands and um and and things
like the brain don't developuntil the 19th or 20th week
anyway.
So you know a lot of, a lot ofthings can't be picked up
earlier.
People say why wasn't itdetected earlier?
It's like it physically cannotbe detected earlier.
(26:41):
In my research role I interviewwomen who have fetal anomalies
and who want whole exomesequencing and we do trios and
some of these are picked up verylate in pregnancy and it's
pretty heartbreaking foreveryone involved.
But depending on where they are, they can still access
termination, depending on thedoctors and the rules in their
(27:04):
state.
I don't think anyone's beendenied termination in their
state.
But sometimes the methods oftermination vary and, for
instance, if someone wants asurgical termination after 20
weeks, there are many statesthat won't do surgical and will
just do induction of labour.
So you might have to fly toanother state if your preferred
method is surgical umtermination.
(27:25):
So I I really believe womenshould have a choice about this,
but it's still not, as there'sstill not as much choice as we
could have okay, and so youmentioned whole exome sequencing
and in like a prenatal settingand using a trio methodology.
Matt Burgess (27:48):
So just to explain that it's looking at the baby,
but we're also doing so in thecontext of mum and dad.
So, being a trio, it's mum, dadand baby.
Sarah Long (28:00):
Yeah.
So what we're looking at isdoes baby have any genetic
changes that would explain thephenotype, the clinical picture
we see on ultrasound?
Are these inherited from themum or dad?
Are mum and dad carriers?
Is it inherited from one parent?
Is dad a carrier or mum's acarrier?
And this is a dominantcondition, meaning mum or dad
might be affected and it mighthave health implications for
(28:22):
them.
Or is this de novo?
Like we mentioned before, isthis a new thing that happened
in the baby?
And all this information notonly helps for future
pregnancies and for the healthof the parents, it also helps us
classify variants.
So if we find a VOOS a variantof uncertain significance in the
baby, but it's in a gene thatmatches up with their clinical
(28:43):
picture, and we see that neitherparents have this VOOS, it
gives us a bit more evidencethat that gene change might be
the thing that's causing theproblems in the fetus.
Matt Burgess (28:54):
Wow, and how quickly can you do this test in
a prenatal setting?
Sarah Long (29:01):
It varies between states.
Some labs can turn it out inabout 10 days, others take about
three to four weeks.
Matt Burgess (29:08):
Um, it's really variable, but um, I think our
average for the research studyI'm on is 17 days wow, okay, so
as interesting as all of thereproductive issues and themes
have been to discuss, a littlebirdie told me that you are
(29:30):
sometimes referred to as thequeen of MTHFR and this is a
little topic that I wanted tohave a little chat to you about.
I know that you published apaper God, it's nearly like 10
years ago now, I think um sevenor eight years yeah, um, about
this, this gene.
(29:51):
So the gene is called mthfr andum, I feel like as a genetic
counselor, we get a lot ofreferrals, that, and it's just
kind of as, most of the time,completely inappropriate and
it's not relevant to somebody'shealth, but a lot of GPs and
(30:15):
naturopaths seem to be orderingthis test.
I know I had, um.
You know, a friend of thefamily had a family member that
is really struggling with like asevere case of clinical
depression and one of the thingsthat was said was oh, and you
know they've got a mutation inMTHFR.
(30:36):
It's like, oh, I don't thinkthat's relevant and it's not
sort of yeah.
I just don't think it's just notrelevant.
But can you tell me a littlebit more about the motivation
for writing this paper and sortof you know why this paper has
been so popular for you?
Sarah Long (30:57):
This paper was done after I was working in prenatal
and general at the time and wewere getting bombarded with
MTHFR referrals for everythingfrom miscarriage to depression
to colorectal cancer, and I wasgetting so frustrated and it
really came to a head one daywhen I had a duty call and this
male patient rang in and he wasvery jovial, he was American.
(31:20):
He said, oh, I need genetictesting.
My sister's got a gene change.
And I said, okay, no worries,we should be able to help you.
Can you tell me a bit more?
And he said, oh, she's hadthree miscarriages and she's got
an MTHFR mutation.
And I said well, I've got somegood news for you, and that is
these polymorphisms.
It probably won't be apathogenic mutation, it's
(31:45):
probably a polymorphism and theydon't cause medical issues, so
it's probably not the cause oftheir miscarriages.
And I explained to him why thatwas.
They only affect enzyme levelvery slightly.
He got really irate with me.
He got absolutely furious wewouldn't test him and I tried
everything.
I said to him what would you dodifferently if you found out
you had this gene change?
And he said I'd eat more folateand I sort of was like okay,
(32:09):
and I tried explaining it to himand then he got quite
aggressive and started yellingat me and saying you're not a
doctor, what do you know?
You're not a doctor.
And that just got me so mad notat the patient but at the
misinformation that I was likeI'm going to write a paper.
I'm going to literature reviewthis.
(32:29):
I'm going to write a paper andthe next time somebody comes to
me I'm going to email them mypaper.
And in the years sincepublishing that paper I've had
so many people reach out to me.
I've had journalists reach out.
I've had lots of patients reachout.
I had a patient who contacts meevery few years from Victoria
and she had really bad clinicaldepression and she was told it
was an MTHFR mutation from anaturopath and she still didn't
(32:54):
feel better after taking thepricey vitamins they sold her
and she felt like it was a sortof a moral failing of her own
that she wasn't better, that shewas doing everything.
And when she read the paper shereached out and said it was a
huge validation for her and shefeels ripped off by her
healthcare provider.
But she just stayed in contactwith me and occasionally would
(33:16):
message how she was going and Ireally felt proud that she'd
gotten some information and shecould see that it wasn't
anything she was doing wrong.
It was just not good healthcareinformation.
Um, there's been some reallyworrying associations with mthfr
.
There's a very popular websiterun by an american who claims
it's linked to bedwetting,claims it's linked to autism.
(33:39):
Um, there's one doctor inamerica who's claimed it makes
people transgender, which isincredibly concerning.
Um, because this particulardoctor is prescribing certain
vitamins to make people not betransgender, which is really
morally, ethically reprehensible.
(34:00):
I just can't stand the idea ofusing junk science to hurt
people in that way.
So, yeah, the paper wasbasically written because I was
frustrated with the lack ofinformation and I wanted to get
to the bottom of it myself.
So I did a lit review and Ifound loads of papers with
associations between differentmedical conditions and these
(34:23):
polymorphisms.
But the science was really bad.
Matt Burgess (34:26):
When you actually looked at how the studies were
done, they they weren't relevantwow, okay, and I think that
that is so important because youknow that case that you had
with that lady.
It sounds like her medicalpeople sort of really failed her
and she was really upset withthat and, um, I don't know.
(34:50):
I think it just highlights thefact that everybody can order a
genetic test, or anybody canorder a genetic test.
But, you know, is it the righttest for the right person, and
are we having people sort ofexplain it that actually
understand what it means?
Sarah Long (35:05):
I think the biggest problem is that it's on.
It's on medicare, but if youlook at the medicare item number
, you can only order mthfr, if I, if my, if I remember correctly
, it's something to do withclotting disorders, so it should
.
Or for homocysteine orsomething, so it shouldn't
actually be on medic like the.
The reason naturopaths anddoctors order with clotting
(35:25):
disorders or for homocysteine orsomething, so it shouldn't
actually be on Medicare.
The reason naturopaths anddoctors order this is not
anything to do with clottingdisorders, it's all these other
reasons, so it shouldn'tactually.
It's not an appropriate test tobe covered by Medicare and,
yeah, I really think forpolymorphisms especially, we
shouldn't be able to have thattest covered by the government.
Matt Burgess (35:45):
Well, excellent.
On that note, I think I'll saythank you very much for your
time today.
It's been really interestingsort of going through these
issues with you, and I wish youall the best with finishing your
PhD.
Sarah Long (35:59):
Thanks.
We've just got a paper acceptedwith minor revisions, which is
the last chapter in my thesis,so hopefully by the end of this
year I'll have that doctor infront of my name and we'll be
done and dusted.
Matt Burgess (36:11):
Excellent congratulations and I look
forward to seeing Dr Sarah nexttime I see you in person.
Sarah Long (36:17):
Thanks, matt.
Matt Burgess (36:18):
Okay, take, take care, bye.
Hello and welcome to Demystifying Genetics podcast
.
My name is Matt Burgess and Iam your host.
I am a genetic counsellorliving and working in Melbourne,
australia.
In this episode, which isepisode one of season four, I
speak with genetic counsellorSarah Long in Perth, western
(00:21):
Australia.
Join us for an interesting chatabout her research and clinical
genetic counselling dilemmas.
Hello, sarah.
Sarah Long (00:32):
Thanks so much for having me.
Matt Burgess (00:34):
Welcome to Demystifying Genetics.
It is episode one of seasonfour.
I'm really excited.
Sarah Long (00:41):
Yeah, I've actually spent the afternoon listening to
some past episodes, so I had abit of an idea what to expect oh
good, and I can see that you'resitting in the sun at the
moment.
You're outside and enjoying thethe sunshine yep, I'm based in
Perth in Western Australia andit's about 25 degrees, so it's
absolutely perfect oh beautiful.
Matt Burgess (01:02):
I'm inside in my study and I've got my beautiful
dog Banjo next to me and I justhope that he doesn't see the cat
next door and start barking.
Sarah Long (01:10):
Well, I've got Loki, who's my puppy, out here and
before he decided to scare offanother dog so he was going
absolutely off.
So hopefully he doesn't arc upeither.
Matt Burgess (01:22):
Well, it's a very dog-friendly podcast, so that is
fine.
I'm really excited about ourconversation today.
I would like to talk to youabout all things reproductive
genetic counselling and Iunderstand that is the topic of
your PhD.
Sarah Long (01:39):
Yeah, so my PhD is about non-invasive prenatal
testing using platforms likeholoxone sequencing to look for
hundreds or thousands of geneticconditions in pregnancy, and
that basically started when Istarted, when I was working in
prenatal for the public hospital, and it was.
Nipt was quite new, but italready evolved into doing
(02:03):
things like microarrays and withthat became a lot of
controversies with positivepredictive values and problems
like that, because the PPVs weremuch lower for micro deletions
and micro duplications and itstarted getting me thinking well
, what happens when we combineit with other technologies and
we can start testing for singlegene disorders on a population
(02:25):
level?
What will happen then?
And that's really where the umimpetuous for doing a phd came
from.
It was a hypothetical uh-huhokay.
Matt Burgess (02:35):
So for the non-genetic counselors listening
to this podcast, I think I'mgoing to break down what you've
just said.
So I think maybe just startwith okay, we talk about NIPT.
I know at work sometimes Irefer to it as NIPS or NIPS.
Could you sort of justbasically explain what this test
(02:55):
is and how it's used?
Sarah Long (02:59):
Absolutely so.
It's a screening test.
It's not a diagnostic test,which is really important to say
and basically it takescell-free fetal DNA, so DNA from
the fetus that's floatingaround in the mother's blood,
and it compares the maternal,the mother's DNA to the fetus's
DNA to see whether there's anyextra or missing bits so you can
(03:21):
tell whether a baby might havetriathlete 21 or Down syndrome.
But you can also look forsmaller parts of the chromosomes
that might be missing orduplicated that can cause
problems like Angelman syndromeor Carter-Willie syndrome, and
you can do that across the wholegenome now.
So you can look forduplications and deletions
across the whole genome.
And in the last couple of yearsa big company has actually
(03:44):
released a test that now looksfor single gene disorders.
The last time I checked therewere 25 single gene disorders on
this list that you could bescreened for in pregnancy.
So my hypothetical of having atest that could screen hundreds
or thousands of geneticdisorders really isn't that far
away commercially.
Matt Burgess (04:04):
Yeah, yeah, I know , I just spent a few years in
the United States and I workedfor a company over there that
had a single gene NIPT test.
So, yeah, very interesting.
And I guess the other thingthat I sort of just maybe we can
define before we move on ispositive predictive value or PPV
(04:26):
.
Yeah, what does that mean to alayperson?
Sarah Long (04:31):
Yeah.
So one of the big problems whenNIPT first came out was it was
advertised as 99% sensitivityand a lot of people doctors and
patients took this to mean 99accurate.
Now a screening test.
You don't use accuracy becauseit's not a diagnostic test.
(04:51):
It's not saying if we say thisperson has down syndrome, 99 the
time it's correct.
What it's saying is that ifthere's a population of 100
people and they all have ascreening test positive for Down
syndrome, then 99% will bedetected and one won't be
(05:11):
detected.
And the other side of that isspecificity.
Sorry for stumbling over that.
And that's saying if we have100 people who have a baby with
Down syndrome, how many will bepicked up?
And we know that specificity isreally good for NIPT.
It's over 90% but it's not 100%.
(05:33):
So it doesn't detect allpregnancies with trisomy 21.
And I'm using trisomy 21 orDown syndrome as the example
because that's the conditionthat has the highest sensitivity
and specificity.
When you start looking at microduplications and dilations, it
drops quite low and when youlook at things like the sex
chromosomes, it drops quite lowagain.
Matt Burgess (05:54):
Um, some of the sex chromosomes has have a
positive predictive value of the50 kind of thing yeah, when I'm
speaking to women and couplesabout this test or this screen,
um, like I, I think of myselfand I think you know I am a
genetic counselor and part ofour role is to to give people
(06:18):
information and to explain it,and obviously we know much more
about the test and part of ourrole is to just give as much
information as the patients needin order to make their decision
.
But, on the other hand, I kindof think sometimes, like when it
comes to my own sort ofpersonal medical information,
like I don't know, likeignorance is bliss or you know,
(06:39):
like I am very happy for thedoctors and medical staff to be
quite paternalistic and say,like Matt, do this or don't
worry about this.
And I really struggle because Ithink it's completely
understandable when someonecomes in and says how accurate
is this test, and we kind ofknow what they mean.
(07:01):
But it is actually quitedifficult to kind of really
break down Like you don't wantto give somebody a statistics
lesson and you know, I don'tknow, is that something that you
kind of have got a better with?
That sort of explaining?
Like if I said, oh, howaccurate is this test in a
clinic, how do you sort ofexplain that?
Sarah Long (07:27):
this test in a clinic?
What?
How do you sort of explain that?
So the interesting thing is Idon't work clinically in
prenatal.
I work clinically two days aweek in familiar cancer and I
work three days a week in aresearch position doing prenatal
.
And even if I did workclinically prenatal at the
public hospital I work at, wedon't see people before their
NIPT tests.
We only see them after they'vehad a diagnosis confirmed on
(07:49):
amnio and then we do thecounselling because of the sheer
volume of NIPT that's beingdone in the general population.
So I think that there is a lotof misinformation about how NIPT
works, because I don't thinkthat a lot of general doctors
understand the difference inbetween a screening and a
diagnostic test, although Ithink it has gotten better.
(08:10):
When NIPT first came in inWestern Australia we had
patients who were ending theirpregnancy based on the NIPT
results before havingconfirmation with amnio, and we
quickly communicated to doctorswhy that was inappropriate.
So it's not something I have todo on a clinical basis very
often, um, it's something that Ido as part of my phd and it's
(08:34):
something that I've been doing.
Um, when I talk to patients inmy research role, they often
bring up their niptT results andask questions about them.
Matt Burgess (08:50):
Yeah, I think that's difficult in research
when you're sort of interviewingpeople and then they have like
a clinical question.
It's like, oh, you know, there'sa bit of a fine line there with
sort of being able to answerthe question.
But I think you bring up areally interesting point about
pre-test counselling andpost-test counselling and
post-test counselling.
And you know, in geneticcounselling it wasn't that long
ago and I mean, there's probablystill people out there that do
(09:13):
that, that do this, where theyspend an hour with a patient
talking about the pros and consof testing one particular gene,
and it's kind of like those daysare gone now.
I think you know like, um, itwasn't that long ago that we
were sort of the gatekeepers ofgenetic testing and like all
(09:36):
genetic testing went throughgenetics and, um, now it's kind
of like every specialty isordering genetic testing and a
lot of people aren't gettingthat pre-test counselling.
And is there a way that you andlike the genetic counsellors
you work with can seefacilitating that?
(09:58):
Like, you know, not everyonecan sit down, but, you know, can
we record a video?
Or, you know, can we get peopleto have a fact sheet?
Or, you know, can we empowerthe general practitioners to
sort of give more informationbefore the test yeah, well,
there's been a few things.
Sarah Long (10:15):
So we've had mainstreaming come in for
ovarian cancer testing inwestern australia.
Um, it's coming for cancertesting, but the doctors and the
surgeons, the oncologists, havebeen a bit more reluctant,
because I think at the startthey were quite keen.
They thought, oh, instead ofwaiting for a few months to get
a test result, I can just orderit and be done.
And then the first lot ofbooths came back and they all
(10:38):
panicked and went why are wedoing this?
We don't know what this means,send it to genetics.
And then, of course, they startdealing with the ethical issues
involved and I think they'vereally backed off and they're
sending way more to us becauseit was, I think they realised
that it's a lot more complex andthey don't have the time to do
a lot of the counselling.
But what we've done is done alot of education, done a lot of
(11:04):
talking at multidisciplinarymeetings about how to facilitate
testing and what are some ofthe issues involved.
We also developed a consentsheet and the consent ticks off
a lot of the issues that shouldbe discussed in pre-test
counselling.
So if they go through theconsent properly, they should
have had the basic issuescovered, if that makes sense.
So, yeah, that's really helped.
(11:28):
I think in some cases thepre-test counselling isn't as
important as in others.
So what I mean by this is, witha lot of the ovarian cancer
patients, they're usually a lotolder, so we're talking women in
their 80s or 90s.
For a lot of them, they'vealready had their children.
They might not have a lotlonger to live, so it's not
(11:51):
about other cancers that mightpop up in future.
A lot of these are quite latestage cancer patients and the
main reason they're having thetesting is for treatment
purposes, so they can take PARPinhibitors for their ovarian
cancer if they're BRCA1 or BRCA2positive.
So I think that's reallydifferent for when you're seeing
a 40-year-old for breast cancerwho's got two young children
(12:15):
and brothers and sisters andthey're worried about the impact
on their family and what it'sgoing to mean for them.
So I think it's the context aswell as to whether mainstreaming
is appropriate or not in thosecircumstances.
Matt Burgess (12:31):
Yeah, and I think that makes sense.
But what I really like or whatI take away from that is the
value of genetic counsellors.
On one hand, I think evenworking in like a big public
hospital, you know, with a largeclinical genetics department,
(12:51):
there is still a lot of workersthat do not know what a genetic
counsellor is or what we do.
Or you know sort of what ourtraining is, genetic counsellor
is or what we do, or you knowsort of what our training is.
But when the doctors out therekind of requested that they be
able to order their own genetictests and then we helped
facilitate that through likethis mainstreaming sort of
concept, and then all of asudden they were like, oh,
(13:14):
actually this is a bit harderthan what I was expecting.
It's sort of I don't know ifheartwarming is the right word,
but you know like it'sencouraging to hear that they
value genetic counselling andthey can see that we can
actually help in the process andthe management of their
patients.
Sarah Long (13:32):
Absolutely and I think that's really come out.
They do value us.
We've had we started attendingMOLS years ago and they've
started up a few more meetingsaround Perth.
I'm involved in the breastcancer ones and the latest time
they started one up theyspecifically requested a genetic
counsellor join them.
So they are recognising ourvalue in multidisciplinary
(13:55):
management of patients withcancer.
We've also got renal andcardiac genetic counsellor
specialties working at thepublic hospital now and they
work very closely withcardiologists and renal
specialists.
So we are expanding into otherareas where these specialists
are saying we need geneticsinput, we need a genetic
counsellor on board.
Matt Burgess (14:14):
Yeah, and I guess you know when you order a
genetic test, I think you knowthe layperson would be familiar
with the test either coming backpositive or negative.
But you mentioned the word VOOSand just to sort of explain
that that means a variant ofunknown significance.
So sometimes when we do genetictesting the lab may find a
(14:37):
change in the gene and weliterally do not know what it
means, or there's not enoughevidence to say that that is
actually disease causing or not.
And yeah, it's been myexperience as well that some of
the doctors you know, as soon asa variant of unknown
significance comes up, they'relike oh, I don't know how to
(14:58):
manage this.
Sarah Long (14:58):
Like, oh, let's sort of handball it back to genetics
absolutely, and I think vocesor variants of unknown
significance are definitely thebane of genetic counselors
existence.
Um, it's hard to communicate topatients.
It's hard to communicate topatients family, who might just
hear there's something found ina gene and then they contact us
wanting testing.
And even doctors sometimes makeclinical decisions based on
(15:24):
VUSAs and we've had to go backand tell them that's really
inappropriate.
This is not a clinicallyactionable gene change.
But yeah, there's definitelybeen antidotal cases of people
having prophylactic surgerybecause of VUSA and stuff like
that.
Matt Burgess (15:39):
Okay.
So I'm a bit surprised that wewent into cancer.
I didn't think that we would betalking about that today.
Sarah Long (15:47):
Yeah, so my PhD is actually mixed methods.
It's qualitative andquantitative.
We started out by deciding toget some basic ground-level
knowledge about women andgenetic conditions, and lots of
conditions, whether people withchildren with genetic conditions
would have wanted to know.
(16:07):
So we did.
I did, uh interviews with 30women 10 who self-identified as
healthy with no children, 10 whoself-identified as healthy with
healthy children and 10 whoidentified as healthy with
children with a de novo geneticcondition that wouldn't have
been picked up in pregnancyusing the technologies available
(16:27):
at the time of the interview.
Matt Burgess (16:31):
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But going back to sort ofreproductive and sort of what
(17:17):
your research has been in ofreproductive and sort of what
your research has been in, youknow I kind of consider myself a
qualitative researcher and sortof one of my favourite
approaches is using aphenomenological approach.
I always have to be carefulsaying that big word and I think
that that's sort of yourapproach as well.
(17:40):
Can you tell us a little bitmore about sort of the different
studies that you've done usingqualitative research?
Sarah Long (17:49):
Neither parents are carried.
It happens in the egg or thesperm before conception and then
when they join up together, thechild has a genetic condition
that neither parent's thecarrier's on.
So even if the parents hadundergone carrier screening
before conception, this is notsomething they could have
prevented in any way.
And what did you find?
We found a lot of things.
(18:10):
We published quite a few paperson the qualitative data.
There was actually quite goodgenetic literacy among all the
cohorts, although the cohortswith women with genetic
conditions had a lot moreknowledge about genetic
conditions in general because ofexposure to support groups.
And even the women withoutchildren, who tended to be a bit
(18:31):
younger, had quite a lot ofknowledge about genetic
conditions, and some of it wasfrom the media.
So one person had seen grey'sanatomy and said oh you know, I
saw this genetic condition, I'mdefinitely going to get tested
for it.
And another person had seensomething in the newspaper about
a couple with a child with craba disease and she was adamant
(18:53):
she was going to get tested forcrab a disease because it was a
really heartbreaking story.
So that was quite interestingto hear the exposure people had
to different genetic conditions.
It was really interesting thatnot a lot of people knew what
they had been screened for ifthey did have children.
So a lot of them said, oh, Ihad screening for Down syndrome,
but they weren't really awarethat there were other things
(19:17):
screened for and they weren'taware that you could get other
things screened for, and theyweren't aware that you could get
other things screened for,especially before pregnancy as
well.
Um, probably the mostinteresting paper is would I
have wanted to know, which isabout the experiences of the
mums that had children with denovo genetic conditions, and I
(19:37):
asked them would you have wantedto know about your child's
genetic condition while you werepregnant?
And about half of them said yes, I would have wanted to know,
because this is a really hardlife and I probably would have
ended the pregnancy.
So that was quite brutallyhonest.
And half of them said no, Iwouldn't have wanted to know,
because I probably would haveended the pregnancy and they've
brought so much joy and richnessinto my life.
(19:59):
I couldn't imagine my lifewithout them here.
So it was a really interestingperspective and one that raises
the ethical issue of if we dostart screening for more
conditions.
Are we stigmatising people withdisability and are we doing
them a disservice by enablingpeople to end these pregnancies.
That might be individuals wholead really rich, fulfilling,
(20:23):
joyful lives despite the factthey have genetic conditions.
And on the flip side to that is, I believe every child should
be a wanted child, no matterwhat the circumstances.
And if a parent feels theycan't parent a child with a
severe genetic condition, thenwho am I to say you shouldn't.
You know, this child might havea great life.
(20:44):
You should parent this child.
So it's.
It's one of those conundrumsthat has come up in my PhD that
I've I've written about and Itry to acknowledge in all my
discussions, but I don't thinkthere's an easy answer question,
but I don't think there's aneasy answer.
Matt Burgess (21:05):
Wow, there's so much there.
Yes, I, and one of the thingsthat we sort of touched on
before was that you know thesenewer sort of versions of the
non-invasive prenatal screen.
Um is looking at conditionslike micro deletions or sort of
uh rarer changes that can occurin our genome and that the
positive predictive value isn'tthe highest for this um.
(21:29):
So I guess practically whatthat means is um women could
have these tests.
It comes back increased riskand then um, it's actually not
the case in the child.
You test the child.
Um test the fetus and the.
They do not have the conditionthat um was brought up on on the
(21:52):
test.
What did women?
Did women sort of talk to youabout their feelings, about, you
know, conditions being included, whether sensitivity wasn't
that high?
Sarah Long (22:04):
So at the time that I did the test, none of the
women sorry the interviews noneof the women were pregnant and
had NIPT.
Most of the women had firsttrimester screening because it
was still when NIPT was quitenew.
So we asked about what theythought about NIPT.
In the quantitative study,which was the larger online
(22:25):
study that we generated thequestions from themes identified
in the qualitative study, but Ididn't ask directly about what
they felt about NIPT.
Having said that, a few yearsago a friend reached out and
said I've just had this Harmonybook.
I don't know whether I canreached out and said I've just
had this harmony I don't knowwhether I can say the name,
sorry, I just had this NIPT testand it's come back saying the
(22:45):
baby has 22q11 syndrome.
What do I do Now?
Every genetic counsellor knowsthat you don't counsel your
friends.
So I immediately found thewebsite and hooked her up with
the genetic counsellor.
But I did tell her look, look,the positive predictive value is
low.
So this is something that it's.
It's not a.
(23:06):
You know it's.
It's not a hundred percent,it's not a diagnosis.
Talk to the genetic counsellorand then you can arrange an
amniocentesis if you want.
And um, she talked to thegenetic counsellor associated
with the company and she had areally good experience with them
, which was great.
I think they told her thepositive predictive value was
(23:26):
around 40%, so that really puther mind at ease.
And then I actually went withher to the amniocentesis because
her partner had to look aftertheir other children look after
their other children.
So I was there to hold her handand watch my 800th amnio go
through.
(23:47):
It's a bit different when it'syour friend on the table, though
I was much more nervous than Iusually am and the baby looked
fine.
An ultrasound, no cardiacdefect or anything, and the baby
came back completely fine andhe's actually my godson now.
So that, yeah, yeah.
So so that was lovely.
Um, it was a good.
It was a good outcome, but itwas horrific for my friend who
(24:10):
already had two kids and youknow a 22q11 is so variable and
you can be absolutely fine oryou can have quite a lot of
delay and you just don't get anidea of what would this look
like for me and my family.
So while I haven't had toclinically counsel about it, I
have a quite personal experiencewith it yeah, it is very
(24:36):
difficult.
Matt Burgess (24:37):
I feel like sometimes we can sort of give
the diagnosis and the people youknow, people say what does that
mean?
And that's a really hardquestion to answer zone around
(25:04):
the moment where it just seemsamazing that they're going back
to a law, um from the 1800s,about termination and, um, you
know, having lived in americaand kind of seeing um the
medical system over there andhow complicated it is and how
expensive it is, and then comingback to australia, um, I'm just
wondering about termination andhow easy is it for women to
(25:24):
access termination, relativelyspeaking, in Australia?
Is that something that you cansort of comment on or do you
have sort of thoughts about that?
Sarah Long (25:35):
Yeah, yeah.
So in a paper I'm writing upfor my research.
I don't remember off the top ofmy head I'm writing up for my
research.
I don't remember off the top ofmy head, but basically a lot of
the states require two doctorsafter a certain gestation to
sign off on it.
Wa had some of the mostrestrictive laws where after 20
weeks you'd have to go to aministerial panel of experts who
(25:56):
would say this condition issevere enough so that allow late
termination.
Thankfully our abortion lawshave changed in WA.
You can now go to 24 weeks andhave late termination.
Thankfully our abortion lawshave changed in wa.
You can now go to 24 weeks andhave a termination.
And the reason that this is soimportant is because most fetal
anomalies get picked up at the20-week scan.
So if the limit to abortion is20 weeks in in a state, then
(26:19):
you've got very little or almostno time to make a decision
before that decision is out ofyour hands and um and and things
like the brain don't developuntil the 19th or 20th week
anyway.
So you know a lot of, a lot ofthings can't be picked up
earlier.
People say why wasn't itdetected earlier?
It's like it physically cannotbe detected earlier.
(26:41):
In my research role I interviewwomen who have fetal anomalies
and who want whole exomesequencing and we do trios and
some of these are picked up verylate in pregnancy and it's
pretty heartbreaking foreveryone involved.
But depending on where they are, they can still access
termination, depending on thedoctors and the rules in their
(27:04):
state.
I don't think anyone's beendenied termination in their
state.
But sometimes the methods oftermination vary and, for
instance, if someone wants asurgical termination after 20
weeks, there are many statesthat won't do surgical and will
just do induction of labour.
So you might have to fly toanother state if your preferred
method is surgical umtermination.
(27:25):
So I I really believe womenshould have a choice about this,
but it's still not, as there'sstill not as much choice as we
could have okay, and so youmentioned whole exome sequencing
and in like a prenatal settingand using a trio methodology.
Matt Burgess (27:48):
So just to explain that it's looking at the baby,
but we're also doing so in thecontext of mum and dad.
So, being a trio, it's mum, dadand baby.
Sarah Long (28:00):
Yeah.
So what we're looking at isdoes baby have any genetic
changes that would explain thephenotype, the clinical picture
we see on ultrasound?
Are these inherited from themum or dad?
Are mum and dad carriers?
Is it inherited from one parent?
Is dad a carrier or mum's acarrier?
And this is a dominantcondition, meaning mum or dad
might be affected and it mighthave health implications for
(28:22):
them.
Or is this de novo?
Like we mentioned before, isthis a new thing that happened
in the baby?
And all this information notonly helps for future
pregnancies and for the healthof the parents, it also helps us
classify variants.
So if we find a VOOS a variantof uncertain significance in the
baby, but it's in a gene thatmatches up with their clinical
(28:43):
picture, and we see that neitherparents have this VOOS, it
gives us a bit more evidencethat that gene change might be
the thing that's causing theproblems in the fetus.
Matt Burgess (28:54):
Wow, and how quickly can you do this test in
a prenatal setting?
Sarah Long (29:01):
It varies between states.
Some labs can turn it out inabout 10 days, others take about
three to four weeks.
Matt Burgess (29:08):
Um, it's really variable, but um, I think our
average for the research studyI'm on is 17 days wow, okay, so
as interesting as all of thereproductive issues and themes
have been to discuss, a littlebirdie told me that you are
(29:30):
sometimes referred to as thequeen of MTHFR and this is a
little topic that I wanted tohave a little chat to you about.
I know that you published apaper God, it's nearly like 10
years ago now, I think um sevenor eight years yeah, um, about
this, this gene.
(29:51):
So the gene is called mthfr andum, I feel like as a genetic
counselor, we get a lot ofreferrals, that, and it's just
kind of as, most of the time,completely inappropriate and
it's not relevant to somebody'shealth, but a lot of GPs and
(30:15):
naturopaths seem to be orderingthis test.
I know I had, um.
You know, a friend of thefamily had a family member that
is really struggling with like asevere case of clinical
depression and one of the thingsthat was said was oh, and you
know they've got a mutation inMTHFR.
(30:36):
It's like, oh, I don't thinkthat's relevant and it's not
sort of yeah.
I just don't think it's just notrelevant.
But can you tell me a littlebit more about the motivation
for writing this paper and sortof you know why this paper has
been so popular for you?
Sarah Long (30:57):
This paper was done after I was working in prenatal
and general at the time and wewere getting bombarded with
MTHFR referrals for everythingfrom miscarriage to depression
to colorectal cancer, and I wasgetting so frustrated and it
really came to a head one daywhen I had a duty call and this
male patient rang in and he wasvery jovial, he was American.
(31:20):
He said, oh, I need genetictesting.
My sister's got a gene change.
And I said, okay, no worries,we should be able to help you.
Can you tell me a bit more?
And he said, oh, she's hadthree miscarriages and she's got
an MTHFR mutation.
And I said well, I've got somegood news for you, and that is
these polymorphisms.
It probably won't be apathogenic mutation, it's
(31:45):
probably a polymorphism and theydon't cause medical issues, so
it's probably not the cause oftheir miscarriages.
And I explained to him why thatwas.
They only affect enzyme levelvery slightly.
He got really irate with me.
He got absolutely furious wewouldn't test him and I tried
everything.
I said to him what would you dodifferently if you found out
you had this gene change?
And he said I'd eat more folateand I sort of was like okay,
(32:09):
and I tried explaining it to himand then he got quite
aggressive and started yellingat me and saying you're not a
doctor, what do you know?
You're not a doctor.
And that just got me so mad notat the patient but at the
misinformation that I was likeI'm going to write a paper.
I'm going to literature reviewthis.
(32:29):
I'm going to write a paper andthe next time somebody comes to
me I'm going to email them mypaper.
And in the years sincepublishing that paper I've had
so many people reach out to me.
I've had journalists reach out.
I've had lots of patients reachout.
I had a patient who contacts meevery few years from Victoria
and she had really bad clinicaldepression and she was told it
was an MTHFR mutation from anaturopath and she still didn't
(32:54):
feel better after taking thepricey vitamins they sold her
and she felt like it was a sortof a moral failing of her own
that she wasn't better, that shewas doing everything.
And when she read the paper shereached out and said it was a
huge validation for her and shefeels ripped off by her
healthcare provider.
But she just stayed in contactwith me and occasionally would
(33:16):
message how she was going and Ireally felt proud that she'd
gotten some information and shecould see that it wasn't
anything she was doing wrong.
It was just not good healthcareinformation.
Um, there's been some reallyworrying associations with mthfr
.
There's a very popular websiterun by an american who claims
it's linked to bedwetting,claims it's linked to autism.
(33:39):
Um, there's one doctor inamerica who's claimed it makes
people transgender, which isincredibly concerning.
Um, because this particulardoctor is prescribing certain
vitamins to make people not betransgender, which is really
morally, ethically reprehensible.
(34:00):
I just can't stand the idea ofusing junk science to hurt
people in that way.
So, yeah, the paper wasbasically written because I was
frustrated with the lack ofinformation and I wanted to get
to the bottom of it myself.
So I did a lit review and Ifound loads of papers with
associations between differentmedical conditions and these
(34:23):
polymorphisms.
But the science was really bad.
Matt Burgess (34:26):
When you actually looked at how the studies were
done, they they weren't relevantwow, okay, and I think that
that is so important because youknow that case that you had
with that lady.
It sounds like her medicalpeople sort of really failed her
and she was really upset withthat and, um, I don't know.
(34:50):
I think it just highlights thefact that everybody can order a
genetic test, or anybody canorder a genetic test.
But, you know, is it the righttest for the right person, and
are we having people sort ofexplain it that actually
understand what it means?
Sarah Long (35:05):
I think the biggest problem is that it's on.
It's on medicare, but if youlook at the medicare item number
, you can only order mthfr, if I, if my, if I remember correctly
, it's something to do withclotting disorders, so it should
.
Or for homocysteine orsomething, so it shouldn't
actually be on medic like the.
The reason naturopaths anddoctors order with clotting
(35:25):
disorders or for homocysteine orsomething, so it shouldn't
actually be on Medicare.
The reason naturopaths anddoctors order this is not
anything to do with clottingdisorders, it's all these other
reasons, so it shouldn'tactually.
It's not an appropriate test tobe covered by Medicare and,
yeah, I really think forpolymorphisms especially, we
shouldn't be able to have thattest covered by the government.
Matt Burgess (35:45):
Well, excellent.
On that note, I think I'll saythank you very much for your
time today.
It's been really interestingsort of going through these
issues with you, and I wish youall the best with finishing your
PhD.
Sarah Long (35:59):
Thanks.
We've just got a paper acceptedwith minor revisions, which is
the last chapter in my thesis,so hopefully by the end of this
year I'll have that doctor infront of my name and we'll be
done and dusted.
Matt Burgess (36:11):
Excellent congratulations and I look
forward to seeing Dr Sarah nexttime I see you in person.
Sarah Long (36:17):
Thanks, matt.
Matt Burgess (36:18):
Okay, take, take care, bye.
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