It’s multiple conditions we group together naively based on surface level symptoms. Same for many disorders.
The type that comes with gender and sexual fluidity, bendyness, ADHD = rccx caused ASD.
Then that will have multiple subtypes based on mutation combination within the rccx module.
(The RCCX module would’ve been excluded from the genetic analysis the report this article is based on - due to its complexity).
Severe/non-verbal ASD is more likely completely unrelated and caused by dendritic abnormalities (reduced or excessive branching, immature spines, disrupted morphology, etc)
You seem to have a more in depth grasp of the precise genetics involved here than I do, what would your opinion be of Dr. Frye’s concept of “Cerebral Folate Disorder” that I mention in another comment?
Here’s a paper from him and his team, he has many though:
As best I can tell, he is focused on the non-syndromic, non-verbal, uh, what this recent paper OP is about seems to categorize as ‘early diagnosis autism’.
He’s got a cluster of specific mutations that produce an evidenced, differing neurochemistry in the brain, and apparently a potential treatment for that ‘subypr/component’ as well?
I… don’t agree with his general description of autism as basically only the kind that makes you developmentally delayed, but, if you can get past that… do you think he may be onto something as far as that being an distinct ‘type’ of autism?
Also, apologies if I am using some terms incorrectly or innacurately, I am not a neuroscientist.
Oh me either don’t worry - CS with a personal interest in genetics/RCCX.
At a (quick) skim, RCCX can set the terrain for Frye’s “cerebral folate disorder” pattern. The block on 6p21 carries C4A/C4B for complement, CYP21A2 for steroid 21-hydroxylase, and TNXB for tenascin-X, with tight linkage and lots of copy-number shuffling.
How this maps to the folate-receptor autoantibody story and folinic response:
C4 structure and dosage can raise baseline autoantibody risk. Higher autoantibody risk makes FRAA more likely.
TNXB variants can track with hypermobility, dysautonomia, and GI dysmotility. Weaker barriers and altered motility increase exposure to food and microbe antigens, which raises chances of receptor-directed autoimmunity like FRAA.
CYP21A2 alleles can shift cortisol and androgen tone. Stress-hormone tone sets immune thresholds and brain energy demand, which makes folate transport failure hit harder.
Put together, you get a terrain with more autoimmunity, more redox strain, and more antigen exposure. That combo can yield low CSF folate with normal serum, especially when FRAA blocks FR-α at the choroid plexus. High-dose folinic acid can bypass via the reduced folate carrier and support one-carbon flux.
Likely RCCX culprits to look at: C4 copy number and long vs short C4 with HERV-K(C4), TNXB loss or TNXB–CYP21A2 hybrid alleles, and common CYP21A2 deficiency variants or pseudogene conversions. (And hope you get lucky - much of RCCX still escapes us) These do not prove causation for CFD, yet they explain why this subtype clusters and why folinic acid helps the FRAA-positive group.
So I’d probably say this (might) be a non-verbal type of ASD caused by RCCX, unlike the type caused by dendritic abnormalities.
… You are much more well versed in the specifics of this than I am, good lord.
Either than or you’re copy pasting an AI response, I have 0 ability to tell, as I … yeah, not even close to an expert on this.
So basically, what you’re saying is… this Folate hypothesis of Frye… seems plausible and could mesh with RCCX… which… are letters that have a meaning I do not know, lol.
I am guessing… recombinant is in there somewhere?
I apparently need an ELI5 for this.
RCCX is apparently different from dendritic abnormalities, which… I assume means something like literally malformed neuron dendrites, maybe kind of like how sickle cell blood cells are malformed compared to non sickle cell?
It’s multiple conditions we group together naively based on surface level symptoms. Same for many disorders.
The type that comes with gender and sexual fluidity, bendyness, ADHD = rccx caused ASD.
Then that will have multiple subtypes based on mutation combination within the rccx module.
(The RCCX module would’ve been excluded from the genetic analysis the report this article is based on - due to its complexity).
Severe/non-verbal ASD is more likely completely unrelated and caused by dendritic abnormalities (reduced or excessive branching, immature spines, disrupted morphology, etc)
You seem to have a more in depth grasp of the precise genetics involved here than I do, what would your opinion be of Dr. Frye’s concept of “Cerebral Folate Disorder” that I mention in another comment?
Here’s a paper from him and his team, he has many though:
https://pmc.ncbi.nlm.nih.gov/articles/PMC5794882/
As best I can tell, he is focused on the non-syndromic, non-verbal, uh, what this recent paper OP is about seems to categorize as ‘early diagnosis autism’.
He’s got a cluster of specific mutations that produce an evidenced, differing neurochemistry in the brain, and apparently a potential treatment for that ‘subypr/component’ as well?
I… don’t agree with his general description of autism as basically only the kind that makes you developmentally delayed, but, if you can get past that… do you think he may be onto something as far as that being an distinct ‘type’ of autism?
Also, apologies if I am using some terms incorrectly or innacurately, I am not a neuroscientist.
Oh me either don’t worry - CS with a personal interest in genetics/RCCX.
At a (quick) skim, RCCX can set the terrain for Frye’s “cerebral folate disorder” pattern. The block on 6p21 carries C4A/C4B for complement, CYP21A2 for steroid 21-hydroxylase, and TNXB for tenascin-X, with tight linkage and lots of copy-number shuffling.
How this maps to the folate-receptor autoantibody story and folinic response:
Likely RCCX culprits to look at: C4 copy number and long vs short C4 with HERV-K(C4), TNXB loss or TNXB–CYP21A2 hybrid alleles, and common CYP21A2 deficiency variants or pseudogene conversions. (And hope you get lucky - much of RCCX still escapes us) These do not prove causation for CFD, yet they explain why this subtype clusters and why folinic acid helps the FRAA-positive group.
So I’d probably say this (might) be a non-verbal type of ASD caused by RCCX, unlike the type caused by dendritic abnormalities.
… You are much more well versed in the specifics of this than I am, good lord.
Either than or you’re copy pasting an AI response, I have 0 ability to tell, as I … yeah, not even close to an expert on this.
So basically, what you’re saying is… this Folate hypothesis of Frye… seems plausible and could mesh with RCCX… which… are letters that have a meaning I do not know, lol.
I am guessing… recombinant is in there somewhere?
I apparently need an ELI5 for this.
RCCX is apparently different from dendritic abnormalities, which… I assume means something like literally malformed neuron dendrites, maybe kind of like how sickle cell blood cells are malformed compared to non sickle cell?
???