Hi,
I was told that this thread had become active again and that it would be a good idea for me to update.
Since I was last here:
It has become clear that there is a high rate of autoimmune disease in patients with ME/CFS and their families. This can be explained by co-inheritance of C4 (autoimmune diseases) and CYP21A2 (acute stress response, enzyme to make cortisol, gene I posit responsible for creating danger response leading to CFS/ME) mutations of the RCCX module. The RCCX module is the only place in the genome where mutations are co-inherited and 10-20% of the population have these mutations.
Naviaux has said that there is a psych profile associated with illness and CFS/ME is similar process to what is going on in autism.
I have been saying this exact thing since early 2016. In fact, that's how the RCCX Theory came about. I believe that the psych profile results from the hormone milieu in utero and in infancy created by carrying CYP21A2 mutations, spiking cortisol with low basal cortisol and high androgens producing an androgenized brain. This psych profile involves a brain wired for danger and sharing qualities with babies born to women pregnant during the Christ church earthquake, exposed to spiking stress hormones in utero: sensory sensitivities, hyperfocus, exaggerated stress response, special abilities, outside of the box thinking and often better than normal stress reaction in most until illness occurs and physical symptoms start to happen at times of any sort of stress (exercise, infection, emotional, etc). The physical responses are due to high CRH, known to be associated with CYP21A2 mutations. CRH activates mast cells and turns on inflammatory cascades.
There have been found to be 2 different populations of people with CFS/ME separated by immune response, comorbidites and cytokine profile.
I posit that one group has CYP21A2 mutation(s) and the inflammation down stream from CRH alone and the other has C4 mutation(s) PLUS CYP21A2 mutation(s) and would have a high rate of autoimmune diseases and possibly hormonally based cancers (prostate and breast) in the family and all of the downstream effects of abnormal complement proteins.
EDS is now officially linked with CFS/ME and Ron Davis's daughter has been diagnosed.
TNXB mutations can cause EDS (considered to be a rare cause), but can also produce subtle findings of connective tissue issues (tongue tricks, flying bird with hands, popping joints, even all over stiffensss I have found to be associated with this psych profile and chronic illness. There are indications that TNXB mutations are rampant in the general population and co-inherited with C4 and CYP21A2 mutations. I have written to Ron Davis many times with no response-the first time in 2015 and this was after seeing subtle signs of this in both Whitney and Ashley in videos (I pointed this out in one of the packets I sent). More about that below.
A GWAS study of the RCCX region demonstrated many of the RCCX comorbidities I have on my list and well-known to be associated with EDS (
http://jmg.bmj.com/content/53/10/681). These include ankylosing spondylitis, psoriatic arthritis. Interestingly, my research partner, Karen Herbst MD PhD has seen a high rate of lichen planus in her adipose disorder patients (she is one of the top authorities on Dercum's-mentioned above- in the world), found with this GWAS study.
Further, there was a big data study showing that many illnesses that I see running in the RCCX familes are related to each-other (running in the same families).
https://medicalxpress.com/news/2017-08-big-yields-diseases.html
Finally, I have had many people with the RCCX phenotype join my FB discussion group and in that group it has become clear that ion channelopathies are rampant, most people have subtle signs of connective tissue abnormalities, the highly sensitive/empath psych profile can become narcissism if the response to it is denial/shutdown. The psych profile overlaps with what is "known" about autism in some ways but not in others (can read people very well as part of danger response, I believe, but is socially awkward as the priority in the brain is to stay safe rather than make friends.) A very high percentage of the women have ring fingers longer than index fingers (indicating high androgen exposure in utero), a high rate of ambidext or left handedness, partially fused 2nd and 3rd toes.
Also, by receiving emails from all over from all sorts of affected people, I have come to find that people with more rare conditions affecting cortisol production, like POR deficiency and CAH from 11beta, also develop ME/CFS.
The RCCX mutations are very hard to study. Mostly, these mutation are not SNP's, rather they are highly complex and varied and not well characterized. Genetic testing with SNP targeting misses them completely. There are copy number variations and non expressing pseudogenes which need to be separated from expressing genes with extensive testing. Getting Ron Davis to contribute his expertise to this end has been my goal from day 1. Karen Herbst MD PhD and I have been gathering observational data for a year and have put together a state of the art questionnaire which is very detailed and will define this phenotype and will also create a rich dataset regarding diagnosis and treatment of a variety of associated chronic illnesses. The plan is to follow-up with questionnaire with extensive RCCX gene testing so that a diagnostic test can be developed which will not require genetic testing of individual patients (we have many physical findings, symptoms and psych questions to define this psych profile). We are writing the IRB Protocol now and will probably release the questionnaire in a month or tow.
Trying to get in touch with Ron Davis has been very difficult. I wrote to him via snail mail, fax, email multiple times in 2015 and said I had this theory and wanted to speak with him. No response till spring 2016 when he wrote and asked for me to send the theory but did not give me a better address. This time sent the theory via snail mail, fax, email and was told by secretary that he had received it. No word back. Heard his daughter has EDS, so wrote again May 2017 with the whole theory, all the same ways. No word back. Karen and I met with Dr. Eric Gordon via Skype twice in June 2017 (the first time with me alone) to talk about the RCCX and our research. Dr. Gordon briefly met with Davis after the first meeting who told him that he hadn't received anything I'd sent. I contacted the secretary and sent again via email and requested confirmation of receipt. She told me he got it. No word. Dr. Gordon sent a summary not emphasizing danger response, the most important part, written by someone else which was not the ideal way to do this because danger response links with Naviaux's findings. No response. I watched the OMF symposium a few weeks back and heard Naviaux say there was a psych profile and this is the same process as autism (I sent him the theory in May 2017 saying this, no response). I then wrote to Linda Tannenbaum and sent her the theory. I received a response that Linda would present the RCCX Theory at the next research meeting. I haven't heard anything else. I am hoping that once the questionnaire is underway that we can make contact. Otherwise, we will hire a commercial lab. I have a bio-informatics company interested in looking at the data initially to show that there may be a signal worth investigating.
That's the story. I hope that answers the questions posed...I typed this quickly between patients.