HI Adreno
If you could post a short list of the known SNPs involved, I'm sure a lot of us would be interested in looking them up on 23andMe.
Great question and one I get often. I need to post a FAQS section on the website when I get a spare moment. I might include some of this answer
I would LOVE to be able to do that, unfortunately, that is where we have to start-we have to match SNPS with with clinical findings (the genes are TNXB, CYP21A2, C4). Also unfortunate, the RCCX which contains these genes is very unique because it mutates often, it is riddled with peudogenes and retrotransposons, it has unique mutations spanning 2 genes and genes travel together, allowing 2 rare diseases to appear in one individual at a much higher prevalence than with region in the genome. Probes for the SNPS which have been so far characterized are available commercially for CYP21A2 (for diagnosing congenital adrenal hyperplasia), TNXB (for diagnosing EDS caused by insuffucient amount of tenascin), not sure about C4 and test kits for a contiguous mutation and several other TNXB mutations can be ordered from a commercial company with the scientist who developed them Wuyan Chen PhD available for comments.
Unfortunately these SNPS are just the tip of the iceberg. 23andme run through analysis will come up with variances of unknown significance, but not even all of them, as analysis of this region involves PCR sequencing and quite a bit of analysis by experts in the RCCX (like Chen). We know about 10% of the population is carrying a CYP21A2 mutation (one of the known ones, known to cause severe enough salt wasting to often be diagnosed early if homozygous), but based on the prevalence of the CAPS profile, I am guessing there is another 10% with variances of unknown signficance (it's similar to the HSP profile which is at 20%). TNXB mutations are in the same boat as they are in the RCCX as well. The characterized SNPS are characterized because they have been linked to haplo-insufficient EDS (AR and AD). This is a rare cause of hypermobile EDS BUT the other mutations will likely cause a wide range of tissue abnormalities from no hypermobility to meeting EDS criteria. We know abnormal tenascin is associated with calcific aortic valves and vesicoureteral reflux, both very common and sometimes associated with hypermobility.
The most that you can do right now is run your DNA through promethease etc and see if it comes up with a known disease causing variant, not likely but I have contacted by LOTS of people (incidentally with all of the "stuff") who were "lucky" like this, or if you have variants of unknown significance, keeping in mind that these services don't have the sophistication to tease apart this region.
Very few geneticists do from my understanding. I didn't understand this when I wrote the "Journal Article" last summer. When I first started working with Karen Herbst MD PhD (she is interested because she sees variable hypermobility and CAPS in her subcutaneous adipose tissue disorder patients at a high rate and she is sure that I am right.), she was confident our university lab would be able to work with the RCCX, now with some samples, we are trying to find out. She is encouraging me to network with geneticists with labs who could definitely do it.
She and I are uniquely poised to do the clinical part of this because I can pick out people with the psych profile and she can figure out what testing needs to be done to demonstrate the hormonal perturbations expected with CYP21A2 mutations. It's not simple testosterone and progesterone, unfortunately. The other issue is that the levels of these hormones are dynamic, depending on whether 21 hydroxylase is overwhelmed or not. We know there is an exaggerated stress response before the enzyme gets overwhelmed and chronic illness starts, so we expect high spiking stress cortisol and low basal cortisol before illness and much lower basal cortisol and still spiking (perhaps) stress cortisol. I also expect low cholesterol and progesterone prior to illness and then high.
In the future, I may ask people from our FB groups (RCCX and Chronic Illness) to send hormone testing they have already had done so we can design this correctly, knowing which tests give a false impression of being negative (like progesterone and testosterone). Anyway, Karen and will be very good at dividing the patients into different groups clinically, even including people with CAPS and no chronic illness (yet) and then we will need a GREAT genetics lab to characterize SNPS.
That's a long answer but it probably answers some other peoples' questions, too!
Also, because our testing is so in depth, we are starting with local (and international for Karen) people from 3 clinics-mine, Karen's and an MD here who treats chronic illness and thinks this theory makes sense of everything she has seen (she treats CERS, Lyme, Toxic mold primarily). I am sure we will need to expand but not for quite a while.