Well, based on what the OP is discussing, the variant CACNAG1 was done by screening 2000 families on an autism chip--basically a huge fishing experiment and might be a calcium ionophore. By the time they get the sequence they can make the genetically modified rodent model and do series of animal tests, like Barnes-Maze and Modified Water Maze, and make some determinations...

I suspect you have some epigenetic phenomena going on moreso in Autism because it is a cross-genetic spectrum disease, rather mono-genetic.

Calcium dysregulation is common in most mental illnesses and neurological illnesses. Last year in Science, they showed there was some effects with Bipolar on the regulation of calcium. However, calcium flux is so transient and removal of stores are under a steady state condition, actual detection of changes are not observed until there is pathology--i.e. that seen in muscle, including cardiac.

Adding EGTA or Thapsigargin in either a cell-based assay or rodent model through osmotic pump, might prove interesting... Functional changes to this gene to vary the variant, may show that either binding to Ca+2 has changed.

But, it looks like in neurons, you are pretty much taking about neural synapses, I guess some form of mitos might be there? IDK? I would have a better understanding if it was SER and muscle.

I hadnt thought of that but thinking back on other illnesses, I think this as a potential reason is quite valid!

AOII Angel, what you've said mirrors almost exactly how I -- with no medical credentials other than a brother who is an MD :D -- have looked at. I agree completely.

I tend to the think of it as a "perfect storm" scenario. My hunch is that there are genetic factors that make a person more likely to end up on the spectrum. Throw in the right combination of environmental factors early in life and the genetic factors are triggered. But with something as varied as autism, I don't think it's going to be one set of genetic factors or one set of environmental factors -- like your cancer comparison, I think it's much more compicated and varied than that.

I think that, as someone who, by virtue of my own family situation, interacts with more parents of kids on the spectrum than the average person might, I was just trying to reflect what I observe about why some parents hold onto the vaccine idea so strongly or are distrustful of what they might call the "establishment." Like I said, I don't agree with them, and I don't see what good is being done by their attitudes, but I can see how they got there. That's all.

Both of these are largely in line with what I've heard from a family member who has a couple of decades of experience working with kids on the spectrum. The vaccination talk, at the end of the day, takes away from research that might actually help find some answers.

ETA: These days you have more experts on autism, more tools (like IEPs) that allow early identification and avoid lumping those on the spectrum with others who have more general learning/developmental disabilities, and in some districts, more of a support system in place to help parents. I think all of those factors help to explain why there are more cases being recognized.

And it leads to kids not getting vaccinated for some pretty serious illnesses.

Yeah, there's that as well...not sure how I forgot that aspect of it.

Wow, I have no idea what you're talking about, but I feel very smart just reading it.