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Genealogy, children, PGD Discuss family and preimplantation genetic diagnosis issues

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Old 29-09-16, 08:42 PM   #1
Ros
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Default Does anyone know about NIPT?

Hi folks, a non invasive method of testing for Downs called NIPT has been in the news today and so I was wondering if anyone has come across it for HD?

It is a blood test that checks for fragments of fetal placental DNA and then sequences it. It says that for some conditions it can be done from 7wks and when I looked into I found a scientific research paper saying it has been used successfully in HD in 2015, but I can't see any reference to it being applied clinically yet.

Has anyone come across it?

I'm currently 8 weeks pregnant. It's my 4th pregnancy and I have two children who don't have HD and had a termination following a CVS in 2011. This pregnancy was unplanned and a complete surprise as my husband had chemo 3 years ago and so we didn't think we could conceive (he also carries HD, not especially lucky medically!).

I'm finding the waiting for the CVS sooooo hard, and even if too late for me it sounds as though NIPT testing would be so much better for others with no miscarriage risk and earlier testing.

Any thoughts would be welcome, Ros x
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Old 30-09-16, 01:43 PM   #2
Allan
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Default Re: Does anyone know about NIPT?

.
Hi Ros

Invasive Postnatal Treatment: the Trials and Tribulations of an hd-day
In amongst my daily workload of attending to his domestic chores; cleaning up spilt food and drinks; rearranging Dental and Social Worker appointments; and listening to his often very interesting, sometimes boring monologues I then have to apply cream today to a very itchy area in my 29 year old son’s scrotal region. Every day is different – but the same awful downhill slide for him.

Anyway, on to: Non-Invasive Prenatal Testing [NIPT] and Huntington’s Disease

The recent research [2012-2015], where it does mention HD with NIPT, seems to add HD in just as a non-specific neurodegenerative disease – to add impetus to NIPT beyond the Down’s Syndrome affiliation to the wider field of Genetic diseases. I have found these NIPT research papers which mention HD:

Non-invasive prenatal testing for aneuploidy and beyond: challenges of responsible innovation in prenatal screening

In the context of prenatal diagnosis of neurogenetic disorders (such as Huntington disease), a form of ‘conditional access’ to testing has been proposed as an ethically acceptable way out of the dilemma between respecting reproductive autonomy on the one hand and protecting the interests and autonomy rights of the future child on the other. Following recent guidelines, the requesting couple should be told that ‘if they intend to complete the pregnancy whether the fetus is a carrier of the gene expansion or not, there is no valid reason for performing the test’. However, this approach seems ill suited to the different context of broad-scope prenatal screening which is not for one specific condition only, nor for conditions that those being tested can be expected to be already familiar with. This concern is also relevant in view of the realistic expectation that non-invasive screening will lead to an increased uptake ‘just for information’. Curiosity on the part of the future parents needs to be balanced with the risk of exposing the future child to possibly harmful information.

Pending further research and debate about the above concerns, there seems to be good reason for not moving beyond ‘serious congenital and childhood onset disorders’ when it comes to the scope of prenatal screening for fetal abnormalities. This can be justified in the light of the normative framework as providing women or couples with meaningful reproductive choices rather than with the (theoretical) option of receiving all information that genomic technologies can possibly reveal about the fetus. This is also in line with findings of attitudinal research among British and Dutch pregnant women. Concerns about wider testing included a slippery slope toward testing for minor abnormalities or cosmetic traits and a trivialization of abortion. Dutch women said they wanted the possibility of testing ‘for severe or fatal disorders that could lead to the early death of the child or a very low quality of life’.

Non-Invasive Prenatal Diagnosis in the Management of Preimplantation Genetic Diagnosis Pregnancies
[Google this title, then download and save]

Huntington Disease
HD is one of the diseases in which our group has more experience in NIPD. The experience in our lab with NIPD of HD comprises 25 cases with a diagnostic accuracy of 68% and a non-detection rate of 28%. Herein, NIPD of a PGD gestation referred for HD diagnosis is shown.

Four maternal plasma samples were collected but none paternally inherited fetal allele was detected with any of the three markers studied. Previous experience in NIPD of HD shows a non-detection rate around 28% [23]. NIPD of HD is basically based on analysis of polymorphic regions (STRs) by QF-PCR. In our experience, NIPD by analysis of STRs is not as successful as other strategies like mini-sequencing or Real-Time PCR. In case of HD, it is also important to consider the number of the CAG repeats of the mutated allele. Since cfDNA fragments have been reported to be around 313 bp, amplification of larger fragments can increase the non-detection rate. In this particular case, non-detection of the paternal/fetal alleles was also observed in NIPD of a previous pregnancy of this couple. This phenomenon could also be related to lower amounts of cfDNA in maternal blood because some unknown physiological conditions of this particular pregnant woman.

Even though no results were obtained from the NIPD study, patients did not undergo conventional PD to confirm PGD results.

As shown in this work, analysis of paternally inherited fetal alleles in maternal blood can be useful for confirmation of PGD results. However, this approach shows two main limitations: (1) detection of maternally inherited disorders; and (2) non-detection of fetal alleles. We have just incorporated the digital PCR technology, a more sensitive technology that will help to improve our diagnosis either by: (1) helping in the detection of maternal alleles, thus being able to diagnose maternally inherited diseases; and (2) increasing the sensitivity rate and having less “non-detections”.

Conclusions
NIPD in PGD pregnancies represents an alternative for confirmation of PGD results for couples
that, after a long IVF process, feel reluctant to undergo conventional invasive PD due to the risk of pregnancy loss. The incorporation of more sensitive techniques (Next Generation Sequencing and Digital PCR) is expanding the scope of non-invasive diagnosis.

***
Obviously, there are no non-scientific plain language easy reads – but it is interesting from a fuller awareness perspective. NIPT seems to be in use in Continental Europe and elsewhere globally - but there is no apparent indication of it being used in the UK.

Other interesting\relevant reading:

Prenatal Diagnostic Testing for Genetic Disorders

Non-invasive prenatal diagnosis of monogenic diseases by digital size selection and relative mutation dosage on DNA in maternal plasma

Genetics Home Reference [excellent guide to all-things Genetic]


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Old 30-09-16, 01:48 PM   #3
lunel78
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Default Re: Does anyone know about NIPT?

Is this the test you mean? My daughter had CVS to check for HD in the baby she was carrying when she was 14 weeks pregnant earlier this year - and also had the following test - array CGH:

Microarray- based comparative genomic hybridisation (array CGH)
www.rarechromo.org/files/Array%20CGH%20QFN.pdf. A new more enhanced test now available for looking at chromosomes is called a microarray-based comparative genomic hybridisation (array CGH) test.

Geneticist spoke to us at length about the results - sometimes you can have too much information. My understanding is that this testing is mainly done on children who present with various problems - and the testing confirms if there is a chromosomal anomaly causing the problems (eg developmental delay, autism, OCD etc).
So there is not a lot of research on prenatal testing where both parents have their blood analysed by array CGH.
Not sure if this is what you mean.

Looks like Allan beat me to it.

The geneticist shared with us the research data being collected worldwide ohttps://decipher.sanger.ac.uk/indexn - if you want to check out Decipher.
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Old 11-06-17, 09:35 AM   #4
Clive
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Default Re: Does anyone know about NIPT?

Hi -
I presume you are asking about detecting HD from the mother's blood after you are pregnant - ie you are not doing PGD - similar how they run tests for Down's etc (something like the Harmony test but specifically for HD. I actually enquired about this direcrly with labs in the US that developed the technique (like Ravgen). It depends whether you are testing for HD directly (you already know if you or your husband is a carrier) or if you don't want to know (indirect/exclusion). If the latter than it is not possible - well it is but extremely costly and time consuming (more than a12 weeks). I have found that picking up the phone and calling these labs is the best way to find out the information and they are usually very helpful.





Quote:
Originally Posted by lunel78 View Post
Is this the test you mean? My daughter had CVS to check for HD in the baby she was carrying when she was 14 weeks pregnant earlier this year - and also had the following test - array CGH:

Microarray- based comparative genomic hybridisation (array CGH)
www.rarechromo.org/files/Array%20CGH%20QFN.pdf. A new more enhanced test now available for looking at chromosomes is called a microarray-based comparative genomic hybridisation (array CGH) test.

Geneticist spoke to us at length about the results - sometimes you can have too much information. My understanding is that this testing is mainly done on children who present with various problems - and the testing confirms if there is a chromosomal anomaly causing the problems (eg developmental delay, autism, OCD etc).
So there is not a lot of research on prenatal testing where both parents have their blood analysed by array CGH.
Not sure if this is what you mean.

Looks like Allan beat me to it.

The geneticist shared with us the research data being collected worldwide ohttps://decipher.sanger.ac.uk/indexn - if you want to check out Decipher.
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