Seeking Common Ground in the Syndromes of Autism
There’s a common saying within the autism community: “If you’ve met one person with autism, you’ve only met one person with autism.” Even though there’s a common core to the conditions collected under this umbrella of a label, it’s a very broad umbrella indeed and spans an incredible array of people. I must admit one of the things which fascinates me most about the conditions is how a single syndrome can manifest both the heights of genius and the dregs of incapacity.
But it’s not only at the behavioral level at which autism’s heterogeneity arises. Just wander over to the AutismKB database and take a gander at the astounding 3,075 genes currently listed. 3,075 genes associated with autism! My God, that’s an overwhelming number. And even though Pinto et al. (2010) have found common ground across genetic functions of proliferation, cell mobility, and Ras/GTPase signaling, any person who goes through that database gene by gene (such as I’ve had the pleasure to do) can tell you that almost any kind of gene you could think of is in there. If one were to equate mutation with changes in local gene expression or function (an unwise assumption), then in the case of autism every part of the cell would somehow be affected. This age of genetics has brought us a staggering amount of information on autism, so much in fact that it’s almost impossible to see the forest for the trees.
The one thing that struck me when studying this vast array of risk genes was precisely that: There’s a VAST number of genes potentially associated with the conditions. Why would so many genes predispose towards autism if they target so many disparate functions? Why indeed.
Unless they don’t, necessarily. In the passing Age of Proteins, the offspring of the Central Dogma of Molecular Biology, mutations have always implied to us some change in local gene function. If a disease condition houses a certain mutation in a certain gene, we naturally jump to the conclusion that the gene product of that gene has somehow been affected and that changes in gene product predispose towards the condition. Simple. But potentially false.
In the case of autism, the fact that so many different types of genes are affected doesn’t suggest to me that all of these gene products are somehow involved in its etiology but that instead they share common traits and perhaps common vulnerabilities with one another. It is their cause which they most conceivably have in common, not their result. If autistics have more mutations, some of them may be involved in development of the condition while others may be inconsequential to it or play roles in other conditions like immune dysfunction, etc.
It is possible that those mutations which arise in genes which target proliferation, cell mobility, and Ras/GTPase signaling like Pinto et al. (2010) had found, may lead to certain changes in brain development which lend towards the conditions. And certainly the research my partner has done focusing on minicolumnar development in autism is indicative of overproliferation of the germinal cells underlying the cortex . At the molecular level, I review in one of my articles, Above Genetics: Lesson from Cerebral Development in Autism, how numerous syndromic forms of autism such as Tuberous sclerosis, Fragile X, and even valproic acid exposure tend to affect related intracellular pathways involved in both cell growth/proliferation and mobility– as well as synaptic development which shares much in common with the molecular process of mitosis. Through these molecular commonalities I could feasibly see a groundwork for development of autism lain which may explain the core symptomatology. Meanwhile, DNA vulnerability across numerous gene types may help us understand how mutations leading to altered functions in these key areas may predispose towards the conditions and likewise tell us why so many different genes are also simultaneously affected. This type of understanding may in turn help us determine when such vulnerabilities are strictly inherited and when they are triggered by exogenous agencies, the latter which may be preventable.
Utilizing Occam’s Razor, which is the least presumptuous? 1) That all mutations across the autistic population lead to changes in gene products which ultimately, somehow, predispose towards the conditions. 2) Or that these mutations share common causes, they have a tendency to occur together, and that only some types of mutations actually lend towards the condition.