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Gentic testing

18 replies

Fluffballs · 11/12/2019 17:45

Hi, wasn't sure where to post this but hopefully someone can help?
My DD has been referred for gentic testing because of a condition she has. I've been given a leaflet but honestly I'm not sure I understand it, and have these questions.

  1. Why does she need it? From the leaflet I gather gentic tests show you where the condition has come from, or if she can pass it on?
  2. The doctor who referred us said HE wanted her to see them, instead of asking if that's something we wanted. Does that mean it's for their research?
  3. Is there a chance it will show up something horrible (future cancers) or do they just look at what they're looking at?
  4. Will the first appointment be a blood test and then we go back a second time for results? How long does that take?

I feel completely in the dark, thanks to anyone who can help.

OP posts:
LeGrandBleu · 11/12/2019 18:42

I have a genetic condition called neurofibromatosis type 1 or NF1 for short.
It is a progressive disorder belonging to the tumour inducing syndromes and I have done years and years of extensive research on it and other genetic disorders. I will try to answer your questions in order.

  1. Why does she need it Some genes have just a function and any genetic damage after birth will have no impact on your health. An example is the gene SOX2 that produces the protein necessary to the development for the eye. If at en embryonic stage, there is a mutation on SOX2, the foetus will not develop normally and the baby will be born without one or the 2 eyes. After the birth and for all your life, if the gene SOX2 is mutated at any point, this will not affect you. Its role and function is done and dusted. You need to consider than we have more than 800 mutations happening per hour, so 10.000 a day, if you prefer, every time a cell divides, reproduces, during the normal cell cycle.

Other genes, like NF1 for example , have a life-long role. Nf1 belong to a family 65 tumour suppressor genes and their role is to prevent tumours and cancer happening in specific parts of the body. In my case it is on nerves, in a case you might be more familiar with , the BRCA1 (Angelina Jolie gene as it is called) , to prevent breast cancer and so on.

Some of the genetic disorder are progressive and that means that there are stages with manifestations that will occur. Now we know enough about epigenetics - what turns a gene on and off - to know that there is a bit of room for intervention, so knowing you have a certain condition might mean you will have more test (MRI for example) or more often or from an earlier age.

My condition comes with a 60% lifetime risk of cancer so I also follow a cancer prevention diet.

Some genetic mutations are dominant, which means your DD will have a 50% to pass the gene, so knowing it, she will have the choice to do pre-implantation gene diagnosis and sleet only the embryos will a healthy gene.

  1. The doctor who referred us said HE wanted her to see them, instead of asking if that's something we wanted. Does that mean it's for their research?

Despite what you might think, there is still a lot we don't know about genes. Up until the ability to do genetic testing not so long ago, people would be diagnosed based on clinical signs in other words, how you look and what problems you have. People would be diagnosed of NF1 based on skin manifestations (cafe au lait macules) for example, but when they started doing genetic testing, a lot didn't have a defect on the NF1 gene but on the SPRED1 gene or the PTPN11 and this meant, they had other conditions.

Because a genetic condition has most of the time a variability in the number and severity of manifestations, having the genetic test done will confirm which condition she has and in some case, give an idea on how it will evolve.

Your doctor might need to see her result to know how better to care for her.

  1. Is there a chance it will show up something horrible (future cancers) or do they just look at what they're looking at?

If you DD has a tumour inducing syndrome you will be given some statistics but these are just numbers and are just mysterious because there is still an awful lot we don't know. Take the BRCA1 for example. It protects you against breast cancer. If you have a defect on it, you have 85% chances to develop breast cancer. What is not understood if why 15 women out of 100 will NOT develop breast cancer and this is where epigenetics plays a role. The gene is the gun, but there are other players that will pull the trigger.

In my case, I am trying to act on my epigenome and prevent further mutations or enhance my immune system .

  1. Will the first appointment be a blood test and then we go back a second time for results? How long does that take?

It really depends on the gene. When I was first diagnosed years ago, there was only one Lab in the world that did the test and it was in Alabama , USA. the test took a bit less than 3 month because I joined a queue. Now, you can get results back in a matter of weeks form labs everywhere. Genetic testing and understanding is changing. But yes, you will have to go back for the results and you will be given more information and probably a care plan.

I hope this makes sense, I have tried to simplify it as much as possible.

The thing to remember, is that depending on which mutation she has, there is room for intervention, and that the epigenetic has a major role.
Happy to answer any further question.

Fluffballs · 11/12/2019 18:57

Thank you for the lovely detailed answer. That helps a lot.
I'm sorry to hear about your condition Flowers

OP posts:
pp12 · 11/12/2019 19:01

I can’t put it any better than LeGrandBleu

I also have NF

LeGrandBleu · 11/12/2019 19:17

It is a very scary moment when you are given the possibility of a genetic condition diagnosis. Some doctors do also a very shitty (excuse my French, I am French) job at explaining what it means.
Most genetic conditions have a charity which can help you understand the implications and meet other people or families. Some are good, others useless as is mine here in Australia.

The knowing - not wanting to know debate is a personal matter. I strongly believe that in most genetic conditions, there is room for intervention.
How much room and how much of a difference you can make can be very little or quite a lot, depending on the gene, if it is only mutated or missing all together which would mean a more severe case.

Research in genetics and epigenetic - (it is a word I have used a lot, so I am going to add a couple of lines to explain how it works. We have the same DNA in every single cell, but not every gene is turned on at the same time, so in your eyes, the INS gene (insulin producing gene) is turned off and this is why you do not make tears made of insulin and the same applies to every part of your body, your blood cells make blood and not bones or skin, your genes receive instructions all the time and what to do and not do, and this means that when there is a mutated gene, the orders can be influenced by the epigenetics which can orders other gene to step in to compensate, shut down other cellular pathway and so in - this is a very complex system ) - is making incredible and fascinating progress. The problem is that there is a 10 year gap between research and change of protocol on how to care for patients, so you will probably need - if you wish to do so and depending on your DD's condition - to stay updated with your own research and I can guide you for that if one day it is something that you would like to do.

I hope your DD's condition is not too severe. Flowers

Fluffballs · 11/12/2019 19:23

Gosh this is a lot of information to take in. You have all clearly done a lot of research, I hope over time I will become as knowledgeable. Right now it all seems like another language, though you both do a great job at explaining. Thank you

OP posts:
lljkk · 11/12/2019 19:24

Gosh, people with NF on MN! I have a close childhood friend who has NF-T2.

OP: how old is your DD? Is her condition something that causes her problems?

Fluffballs · 11/12/2019 19:31

Dd is 7 months, her condition affects her eyes. We don't know to what extent her sight is affected (obviously she can't tell us yet) but I don't believe it to be severe.

OP posts:
lljkk · 11/12/2019 19:47

Ah, I guess doc meant it was info about herself, so she should have right to know when she's an appropriate age.

Does she have epicanthic folds in her eyes?

Fluffballs · 11/12/2019 19:54

No she doesn't.

OP posts:
pp12 · 11/12/2019 19:58

One thing I try and tell people with any genetic condition is to be careful when searching google as there is a lot of fake information out there and some of it can be wrong and makes you panic.

LeGrandBleu · 11/12/2019 20:00

Fluffballs, yes, I did a lot of research on my condition, but also courses on genetics, epigenetics, spent a lot of time on pubmed , and downloaded hundreds of books. But if I am honest, the more I learn , the less I seem to know and the more I realise, some doctors know even less than I do!

In your case, I would first digest the news before hitting the medical literature unless there is an urgency . Something must have triggered your DD's diagnosis and this will be your priority.

When the doctor's suspicion will be confirmed by the genetic test, then yes, you can start looking at the condition. No need to worry now about a disease your DD might not have

SinkGirl · 11/12/2019 20:02

Genetic testing covers such a range - DT2 has had everything from tests for specific conditions, through to having his whole genome sequenced as part of a study. We are still none the wiser. DH and I also are part of the study and we got to choose whether we wanted to know about risks of future disease or things we could pass on but we don’t have results yet.

SinkGirl · 11/12/2019 20:04

Also, twice now doctors have been convinced he has specific conditions based on other diagnoses he has and they’ve been wrong both times. It’s all very complex.

Chocl8 · 11/12/2019 21:24

If it’s helpful to know, our families experience with genetics team has been very positive. My DD has been under them since she was born (now 12). It started with a known congenital issue (so maybe like your DDs eyes?) and some tests were run to rule out things often associated. It was good to rule these out. We then saw a genetic council who took a family history and mainly talked about risk for future pregnancies. My DD continued to have issues popping up and we saw genetics again to have more tests run. We’ve been part of studies (research) but there is always an explanation and consent form for these. My DD is still undiagnosed ie nothing genetic found to make sense of all her issues, but the genetics team keep trying to help. If they can find an answer then there may be an understanding of how to best help in the future. That’s where they are coming from in my experience rather than something sinister. You can ask them questions any time though and you don’t have to consent to anything. HTH.

Fluffballs · 12/12/2019 06:06

Yes @Chocl8 it is congenital (if I'm getting the meaning right, from birth?) But the doctor doesn't think it was caused by something I did in pregnancy, I suppose this might confirm that?
I worry that they might tell me I caused the defect by taking prescribed medication, if that's the case I think I'd rather not know, mum guilt is a killer.

All will make sense eventually I suppose.

OP posts:
LeGrandBleu · 12/12/2019 06:46

@Fluffballs , genetic conditions happen in les than 48 hours and in very very rare cases in the next 24 hours and at the very extreme in 24 more hours of conception and when cell division starts. So you have a very tight 4 day window from fertilisation in which the gene mutation that will cause a genetic syndrome to be present in an human being happens.
Let me explain it better:

Once an egg is fertilised, cellular division begins and it is in this critical first days genetic mutation occurs. Some genes are extremely long and during replication, a tiny letter , one in 3.000.000.000 , is missing, misplaced or similar when copying the DNA. TO give you a concrete example, , imagine you have to copy the entire London phone book every single night, and one day , you only make one tiny error inverting a 3 with a 8, and the person using your phonebook won't be able to reach the person he wants to call. Considering the enormity of the task, it is a very small error, but enough for a message or in the case of a gene, a protein, to be interrupter.

It doesn't take much, the tiniest mistake which can happen and actually happens constantly even as I am typing this, cells in my body divide and do mistakes, but they are repaired or wrong cell is zapped.

It isn't something you did. A genetic condition is an error in duplicating. A genetic condition is bad luck. Full stop.

Then of course there are things that can fail the development of an organ or limb, but this is something completely different, it is the development process that was disturbed either by something external (a drug, a bacteria, an illness such as chickenpox) or by a failure of the foetus because it is a very complex process to go from a cell to a 3.5 kg baby and a lot of things can go wrong.

But let me repeat it: a genetic condition is mostly error in one of our three billions letters that compose our DNA.
And it happens in 24 - 48 hours.

And yes congenital means present at birth, within the gene.

Fluffballs · 12/12/2019 06:58

@LeGrandBleu thank you, that helps.

OP posts:
LeGrandBleu · 12/12/2019 08:10

Apologies for typos, I was in a rush to leave.

I can't stress enough how complicated genetics is and microcellular biology is even worse. Sadly, we are only starting to understand now how it works, but we are barely scratching the surface of a massive iceberg. Scientists don't even agree on the number of genes we have!

Even if we can sequence the whole genome, it doesn't mean we know what every gene does, if the duplications matter, the role of non-coding genes, ....

For all these reasons and hundreds more it is important that you do the genetic test, because what we don't know today, we will hopefully know in 10 years, and gene repair technology has been one of the hot topic of 2019. One day, we will be able to repair the error in the gene with CRISPR-Cas9 or similar

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