Out of curiosity, what leads us to treat ASD as an actual single disorder, as opposed to a billion different individual neurological profiles?

I'd expect one of the things that makes this difficult, too, is that there's a missing component of the "machine" - the genetics affect the pathways, which affect (maybe?) things like signal propagation or network regulation in the brain, but the actual effect of that is on the patient's experience of consciousness, and it's difficult for someone to get more than N=1 of those via commonly accepted legal methods - otherwise, we're all just looking at the outside of the box and saying "huh, this box acts differently than that box, weird."

When autism is discussed as a culmination of denovo mutations, one thing that I dont understand is how this is reconciled with the history of the species.

It seems there is a high rate of mutations, making the non-mutant ensemble incredibly fragile. How did this work in the past? Was there significant selection against mutant varieties?

I thought the US government had just decided that the cause of autism was vaccines </sarcasm>

Here’s how I’m thinking about it (still digging into the details): across genomics, it’s become clear few traits have clear traceability to a few loci in the genome.

Instead, evidence has been growing that epistasis, the nonlinear interaction between genes and other genomic regions, predominates in explanations of most phenotypes.

What this paper does is show where upstream of the genome various combinations of mutations can interact to cause damage during development, thus leading to the phenotype. Rather than correcting a particular mutation, or targeting drugs to their protein products, we may find downstream protein-protein interactions that are strong drivers of the phenotype, and hopefully find ways to prevent/reverse these effects.

Nothing yet. This is incredibly preliminary, with lots of this being tested in frogs.

It hopefully gives hints which will be tested,better understood, and show actual mechanisms in humans. But probably not for years.

There's a CNN article that has some expert quotes for context, but isn't quite as in depth as the study itself: https://archive.ph/yBiM8

I interpret it as they think they can find treatments that will course-correct the development of a child, but they're not saying anything about fixing something that's already broken.