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Mitochondrial disease confirmed!

BeautifulDay

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Can you say what your expertise is in this field? Hobbyist? Undergrad, Masters, Clinical practice?
Me, I was forced into learning genetics from the ground up like many here. I had to fight the stigma of being diagnosed with chronic fatigue for years. I was told all my symptoms were due to stress and I just needed to reduce my stress, get more sleep, not be lazy, and work out harder. Ughhhhh.

So I pushed and read medical literature. Then my kids started getting sick. Very sick. Autistic spectrum and hearing issue, severe lung infections from vocal cord and diaphragm weakness, our youngest started having intermittent foot drop in kindergarten, POTS, stomach and digestion issues, muscle spasticity, terrible headaches, fatigue...... I asked if all our symptoms could be related, but the doctors told me they were all unrelated. I then kept pushing the doctors to look for answers and they kept dismissing me as nuts. Then I found the Mitochondrial issue through my own research and testing. So being a mother on a mission paid off. A top mito clinic is now studying our family.

So to answer you - self taught. I made lots of wrong turns on the way to figuring it out for us. But I couldn't give up. I have gone and still go to the doctors medical conferences and read the original medical journals never relying on any news articles interpretation. I'll read the news articles occasionally to see how they quote the doctor, but it's the studies themselves which have the most important details. Many articles often get the details of studies wrong.
 

pattismith

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BeautifulDay

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@BeautifulDay , do you know a company that would do only a mito-DNA testing ?:thumbdown:

@BeautifulDay has become a top expert in Mito Disease field :)
There are medical labs that just do the Mito DNA. However, the gold standard in recent studies is now WGS or WES (not just of mito genes). This is due to the fact that Mito issues can also be due to non-mito genes. So even the mito specialists are proclaiming WGS and WES. WGS being the best, but WES being more often in budget.

I've seen direct to person labs that offer mito testing. The problem is they often only do a limited number of genes. None of them do all the genes found by the mito specialists so far that cause MitoD. In just targeting the mito genes on some company's panel, it might miss a gene that they don't have on their panel. It's also not much different getting a mito panel versus a WES usually these days.

If an insurance company is going to pay, I suggest pushing for WGS or WES. Of course, it depends upon the fine print in your health insurance policy and if your doctor has a staff that can get things done. Make sure the lab will give you the FASTQ and BAM files (and not just the VCF). If the lab screwed up or if what we know today changes (which it will), it's best to have the data before it was messed with.

I'm not an expert, but like many people here - we often research the heck out of the issues and labs that seem most compelling to answer our questions of why we are ill and what can we do to make ourselves and our family members better. Nobody is going to put in the work that you will.
 
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Yes, and the two other mutations are next to known pathogenic mutations as well :thumbsup:

but none of my mutations have any rs number for now, they are totally unknown.


if you suspect health problems that could match to mitochondrial disease in your mother line, I think it's worth the price.
CFS, fibromyalgia, autism, exercice intolerance, cramps, migraine are among the possible clinical outcome of some mito disease, and mito mutations are rarely investigated by doctors in these problems, so there is little chance that any doc will look for new mutations coding for these diseases.

Promethease is cheaper but will not show you these new mutations, Enlis will do it.


yes, I wish I could see a mito specialist :thumbsup:
Hope you don't mind my asking, but do you know how often Enlis Genomics updates the research on which findings are based (are your results linked to recent study findings)? I was thinking of using it for my own data when I get it, and trialled the program. I like it, and I like how easily you can generate reports from it, but I don't know how 'current' the information is in contrast to Promethease. Since Promethease is cheaper, not knowing this is stopping me from purchasing. I did send the company an e-mail, but didn't get a reply.
 

pattismith

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@Snoozy ,

I can't reply to your question, but I think @BeautifulDay knows more about the update question.

I just know that Promethease was not able to show my 4 missense mutations on my mito-DNA (maybe because they are not known at all, neither with a good or bad repute).
I still don't know if my 23andme datas are right, but these 4 mutations are at one base pair (bp) from known pathogenic ones, and they all are very rare ones.
So if the datas are right, it is likely that some of them are pathogenic.

Below you can see how powerfull tool Enlis is to do some researches in your datas:

I opened some windows with different parameters for targeted researches, and you can see my mutations showing up in the chromosome M
upload_2018-2-26_20-34-7.png
 
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BeautifulDay

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Hope you don't mind my asking, but do you know how often Enlis Genomics updates the research on which findings are based (are your results linked to recent study findings)? I was thinking of using it for my own data when I get it, and trialled the program. I like it, and I like how easily you can generate reports from it, but I don't know how 'current' the information is in contrast to Promethease. Since Promethease is cheaper, not knowing this is stopping me from purchasing. I did send the company an e-mail, but didn't get a reply.
Enlis is like all the companies in the genetics analysis field at the moment. They are all trying to keep up with the magnitude of data coming out. Even the companies that do it just for industry can't keep up. It's an impossible deluge of new studies with new mutations coming out daily. And it's complex. For example, a study might find a mutation is pathogenic, while another might mention that the same mutation was found to be benign. For any company from Promethease to Enlis, none of them have all the mutations and none of them is perfectly accurate because of the complexity and the rate at which the data is coming out daily.

I love Promethease. It's cheap and the people behind it are in it for the right reasons and good folk. Enlis is much more powerful from an analysis point of view. With Enlis it's easy to filter and sort. I start with their analysis of pathogenic and also deleterious mutations that are rare (or near other pathogenic mutation hot spots). If you have multiple family members (or study participants), it's a pretty amazing tool for those of us at home. It's by no means perfect. All of these companies are pioneers and we have to be willing to deal with issues at this early stage (infancy of the industry). When we find errors, most of the companies are very quick in fixing the issues.

So I'm a fan of both and for me it's like comparing apples to oranges.
 
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@pattismith

I ran both the first and second Mitochondrial searches in Enlis that you described and get the exact same 4 mutations show up using my 23andMe data. I'm wondering if others also see the same result and this is an anomoly of the tool, or are we two very rare people? ;)

Here is a screen shot of Enlis using your original analysis tutorial - I see another two more common mutations.

M_Gene_Mutations.png

Has anyone else run this analysis on their 23andMe data with Enlis and if so what did you come up with?
 

BeautifulDay

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@pattismith

I ran both the first and second Mitochondrial searches in Enlis that you described and get the exact same 4 mutations show up using my 23andMe data. I'm wondering if others also see the same result and this is an anomoly of the tool, or are we two very rare people? ;)

Here is a screen shot of Enlis using your original analysis tutorial - I see another two more common mutations.

View attachment 26241

Has anyone else run this analysis on their 23andMe data with Enlis and if so what did you come up with?
It's worth looking into farther. I just checked three people with different mothers who tested with 23andme who are on my Enlis and not one has those mutations. That said, with it popping up for both of you, it's likely to be that 23andme for a time had a bug in their system when calling these mutations. That's usually what it comes down to when unrelated people have the same rare mutations pop up like this. But then again it's worth following through and shaking the tree.
 

BeautifulDay

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@pattismith

I ran both the first and second Mitochondrial searches in Enlis that you described and get the exact same 4 mutations show up using my 23andMe data. I'm wondering if others also see the same result and this is an anomoly of the tool, or are we two very rare people? ;)

Here is a screen shot of Enlis using your original analysis tutorial - I see another two more common mutations.

View attachment 26241

Has anyone else run this analysis on their 23andMe data with Enlis and if so what did you come up with?
Hi @wigglethemouse

It looks like you pop up for a mutation that @pattismith doesn't. The 12501 mutation on the MT-ND5 gene is associated with post-traumatic stress disorder (PTSD). My understanding from the mitochondrial conferences is that those of us with low mito energy issues have an increased risk of things like PTSD and anxiety because the brain sections that deal with emotions and post-traumatic stress need a lot of energy, and when it's low the brain is not getting the energy it needs to deal with anxiety and PTSD.

The MT-ND5 gene is very important in the production of mitochondrial energy. If there is an issue in the gene that's impacting energy in the brain, then it's going to be having an energy issue elsewhere in the body too. The MT-ND5 is important for the mitochondria in every cell in the body. It's just that this study was studying PTSD (not the whole body).

I'm not sure what the full study says or the position it takes, but here it is for your leisurely reading.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4354348/
 
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Thanks you very much @BeautifulDay.

Lots to digest in that paper - talks about CDR and stresses leading to the formation of chronic diseases long after the stressor has gone. Very interesting.

Regarding the 4 x 0.00% allele frequency mutations reported, I did forward my screenshot to Nancy Klimas' team at INIM to see if it could be of interest in identifying a subgroup of patients and told them at least 2 of us have the same 4 mutations. They confirmed they would pass the information on to the researchers of their gene study. I saw this subject mentioned earlier in this or a related thread.
 

pattismith

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Thanks you very much @BeautifulDay.

Lots to digest in that paper - talks about CDR and stresses leading to the formation of chronic diseases long after the stressor has gone. Very interesting.

Regarding the 4 x 0.00% allele frequency mutations reported, I did forward my screenshot to Nancy Klimas' team at INIM to see if it could be of interest in identifying a subgroup of patients and told them at least 2 of us have the same 4 mutations. They confirmed they would pass the information on to the researchers of their gene study. I saw this subject mentioned earlier in this or a related thread.
We are three, because my mother have the same four.

But I feel very confident that they could be a bug from 23andme now that I can see you too have it!

What is important to know is that 23andme changed its snp plateform a few years ago (if I remember correctly, it's 4 years ago), so these four mutations may only show up for people who had their test done on this last plateform.

On the other hand, you put your finger on two other very interesting missense mutations that may be important for you, it was worth doing this screening!
 
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Enlis is like all the companies in the genetics analysis field at the moment. They are all trying to keep up with the magnitude of data coming out. Even the companies that do it just for industry can't keep up. It's an impossible deluge of new studies with new mutations coming out daily. And it's complex. For example, a study might find a mutation is pathogenic, while another might mention that the same mutation was found to be benign. For any company from Promethease to Enlis, none of them have all the mutations and none of them is perfectly accurate because of the complexity and the rate at which the data is coming out daily.

I love Promethease. It's cheap and the people behind it are in it for the right reasons and good folk. Enlis is much more powerful from an analysis point of view. With Enlis it's easy to filter and sort. I start with their analysis of pathogenic and also deleterious mutations that are rare (or near other pathogenic mutation hot spots). If you have multiple family members (or study participants), it's a pretty amazing tool for those of us at home. It's by no means perfect. All of these companies are pioneers and we have to be willing to deal with issues at this early stage (infancy of the industry). When we find errors, most of the companies are very quick in fixing the issues.

So I'm a fan of both and for me it's like comparing apples to oranges.
Thanks for that. :) I suppose not getting a reply made me a little worried that it's not still in active development. It is really nice software, and the ease of generating reports for a specific condition from their sample data is fab. Perhaps I will simply use both.
 

BeautifulDay

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Ok, if I look for mitochondrial chromosome allele frequency less than 1% ... I get a hit. When I add in near pathogenic... I get nothing. No hits.
@aquariusgirl

I looked up the three variants you have for three people with different mothers who I have on Enlis (using their 23andme raw data). Running Enlis on all three shows that all three have the variants for M:14290 and M:15072. That likely means that either 23andme overcalled these locations or Enlis might have the allele frequency wrong for these two spots and they are much more common.

Not one of the three I looked up had the 15,110 mutation
https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?searchType=adhoc_search&type=rs&rs=rs28357685

In this study on LHON, it finds that the 15,110 variant is not pathogenic. Sample #46, G15110A, rs28357685
https://pdfs.semanticscholar.org/8cd2/700814d385e3af40cf059aef13987cad27bc.pdf

Here’s the link to the query on mitomap for the variant
https://www.mitomap.org/mitomaster/view_details.cgi?refp=snvs&query_id=1200825&run_id=1125319
 

BeautifulDay

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We are three, because my mother have the same four.

But I feel very confident that they could be a bug from 23andme now that I can see you too have it!

What is important to know is that 23andme changed its snp plateform a few years ago (if I remember correctly, it's 4 years ago), so these four mutations may only show up for people who had their test done on this last plateform.

On the other hand, you put your finger on two other very interesting missense mutations that may be important for you, it was worth doing this screening!
@pattismith

Automatically your mother or grandmothers to you (or any children you have should have the same mitochondrial variants). They might change over time with age, etc.... - but for the most part anytime you run Chromosome M, only the mom passes it on and it should follow that rule (except for de novo mutations).
 

pattismith

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