Thursday 20 July 2023

Genetic testing results

Click on the picture above to read about the upcoming event in London. There are familiar faces appearing, like Agnieszka, Dr Boles and indeed me.


I am quite often sent genetic testing results. There are many types of tests ranging from inexpensive tests looking at SNPs to the expensive WES or WGS tests.

SNP = Snip = Single Nucleotide Polymorphism = a tiny genetic spelling mistake

WES = Whole Exome Sequencing

WGS = Whole Genome Sequencing

There is a small industry based around selling expensive supplements for SNPs.

We all carry thousands of SNPs and I think these tests may often raise issues that are not causal.  The results from WGS or WES can be much more insightful.  A good example being in the comment recently posted on this blog.


I've been following your blog for many years, it's a real blessing and the perfect place to come and read for us, parents of ASD kids. My boy, 9, has non-regressive autism, is largely non verbal (one word sentence) and has pronounced OCD symptoms (similar to excoriating disorder, but aimed at the environment), hyperactivity and severe gut problems, recurrent vomitting, gastroparesis, etc. The only thing that visibly stopped the hyperactivity and inappropriate laughing and helped him sit for longer periods of time and read his books or watch whole movies was 0.5/kg mg Naltrexone daily, as advised by this paper Lower doses saw the OCD creep back. As for his WGS test results, I've found relevant the fact that he has four pathogenic mutations in the EIF4EBP1, also a de novo mutation in the PIK3R1 gene and multiple other mutations in the STAT3, HTR3a, MAPT and also HLA-DRB1, HLA-DQA1, HLA-A, HLA-B, HLA-C, NRG1, NRG2, SCN4a, CACNA1S genes, amongst many others. We recently tried a course of Azythromycin for immuno-modulation, which saw his OCD reduced further, also his academic interest and focus increased visibly. He responds very well to Ibuprofen, AlkaSeltzer gold, Propranolol, Sytrinol and Cromolyn, but a quite long trial of Bumetanide two years ago did nothing for him. After all trials of various protocols and individual drugs, his gut is still bad, very often food seems to have major difficulty to pass though his digestive tract, no matter how finely tuned his diet is or how many prokinetics he takes. Given your extensive knowledge, I've always wondered what your take on the underlying problem/genetic pathway might be in his case (microglial activation, MTOR activation, perhaps?) and what drugs/cocktail of drugs might work best for his specific genetics and symptoms. He is a smart boy, has self-taught reading, loves music and masters his iPAD like a pro and, unlike what we know about autism, loves being around people. I cannot give up on him. We live in the UK, not the best place to even talk about treatments for autism. Please, if it's not too much to ask, tell me what other medications you thing it might boost his cognition further and help him start talking and develop more skills. Sorry for the long post. And thank you for any advice and ideas you might have to offer.


It would be useful to know which of the above mutations are present in at least one of the parents.  There so many possibly causal mutations here; I expect some are actually not relevant. In other words, it is not as scary at it may appear to be.

I do like to start with the easy part, which will be the ion channels.  Dysfunctions in ion channels (channelopathies) are often treatable with existing drugs and there is a great deal of information on each one.



This gene encodes the calcium channel Cav1.1.

This is known as an L type calcium channel, the other ones being Cav1.2 and Cav1,3 and Cav1.4.

These ion channels are extremely important to how your brain works.  Because they also play a role in how your heart works, numerous drugs have been developed, some are more specific to one type of channel (Amlodipine for Cav1.3, Verapamil for Cav1.2).

The individual channels interact with other sub-types, so a mutation in one sub-type can affect other subtypes.

Very interesting in this case are the GI problems. There were efforts made a few years ago to develop R-verapamil as a drug to treat IBS/IBD under the name of Rezular. Some readers of this blog have reported that the only thing that resolves their child’s GI problems is an L-type calcium channel blocker.

Note Memantine, which is an Alzheimer’s drug that was subject to a very large autism clinical trial in the US.  The trial was deemed a failure, but one reader told me that Memantine is the only drug she had found that solved her child’s GI problems.  Memantine has several different modes of action, and a little reported one is blocking L-type calcium channels.

Conclusions. Our results suggest that the neuroprotective effect of memantine could arise not only through the inhibition of the NMDA receptor current but also through the suppression of the L-type Ca2+ current.   


You might expect/hope a geneticist would suggest treatment with a drug like Verapamil.



This gene encodes the sodium ion channel Nav1.4.

This is one of the genes associated with Hypokalemic Periodic Paralysis (HPP), that was covered extensively in this blog. Interestingly the above Cav1.1 is also associated with Hypokalemic Periodic Paralysis (HPP).

The other genetic cause of HPP is KCNJ2 (an inward-rectifier potassium channel Kir2.1).

The immediate recovery therapy is drinking a potassium supplement.

A common preventative measure is acetazolamide (Diamox). This drug has also been covered in previous posts. The proposed mechanism is that it “increases the flow of potassium” – not sure what that is supposed to mean.

Some common anti-epilepsy drugs block Nav1.4 (Lamotrigine, Phenytoin etc).

All of the above-mentioned drugs have been used in autism. In specific cases they have shown a benefit.

You could ask your doctor to cautiously try them one by one.

Interestingly, the drug that seems to help many with sound sensitivity is Ponstan.  This cheap drug that affects the flow of potassium ions was proposed by Knut Witkowski as a therapy for 2-3 year olds to prevent non-verbal severe autism. 



Here you mention there are 4 pathogenic mutations.

This gene is a real mouthful, but regular reader might recall the odd looking eIF4E part appearing in some previous posts

“This gene encodes one member of a family of translation repressor proteins. The protein directly interacts with eukaryotic translation initiation factor 4E (eIF4E), which is a limiting component of the multi subunit complex that recruits 40S ribosomal subunits to the 5' end of mRNAs. Interaction of this protein with eIF4E inhibits complex assembly and represses translation. This protein is phosphorylated in response to various signals including UV irradiation and insulin signaling, resulting in its dissociation from eIF4E and activation of cap-dependent mRNA translation.”

eIF4E inhibitors for Autism – Why not Ribavirin?


As you can see in the above post there are numerous ways to block elF4E. It is possible that the 4 mutations in your gene EIF4EBP1 could have the reverse effect in which case you would want to activate elF4E, not block it.

On the list, in my post above, is quercetin which is OTC and simple to try.



A mutation in this gene can alter the PI3K/AKT/mTOR signaling pathway.

If this gene is causing a problem you might see some facial features a triangular face, a prominent forehead, small chin with a dimple, a loss of fat under the skin, prominent ears, hearing loss and delayed speech.

A mutation in this gene can lead to SHORT syndrome, which hopefully your pediatrician will have heard of.



STAT3 plays a key role in the immune system and elsewhere.

You can either have too much or too little STAT3.

In lay terms the immune system might end up either over-activated (hence benefiting from Ibuprofen and Cromolyn sodium) or under activated.

The immunomodulatory probiotics prescribed by gastroenterologists might be worth a try.

Lactobacillus rhamnosus GG

Lactobacillus plantarum 299v 


This might well reduce GI problems as well.



This gene encodes subunit A of the type 3 serotonin receptor. It has lots of effects, but it may contribute to the vomiting.

It is associated with:

  • Motion sickness
  • Irritable bowel syndrome
  • Social phobia
  • Serotonin syndrome

For gastroparesis (impaired stomach's motility) the good drug seems to be Domperidone, which you should be able to get for free from your NHS doctor.

Another very popular therapy for gut dysbiosis of all kinds in some countries, but not the UK, is sodium butyrate. This has been mentioned in previous posts. It is an OTC supplement that will produce butyric acid in the gut and it helps restore a healthy mucosa. If you eat lots of fiber and have a healthy microbiome you would produce butyric acid naturally. The cheapest place in Europe to buy it is Poland, where they sell a product called Intesta Max (a weaker version is Intesta).  In the UK it is 3 times more expensive. Making friends with a Pole will save you money.



The MAPT gene makes tau proteins.  There is a class of disease called tauopathy.

Tau Reduction Prevents Key Features of Autism in Mouse Models


Tau: A Novel Entry Point for mTOR-Based Treatments in Autism Spectrum Disorder?


As with the PIK3R1 mutation this will lead you to the idea of targeting mTOR signalling. You can inhibit this with Rapamycin, which has been used in autism.


Rapamycin/Sirolimus Improves the Behavior of an 8-Year-Old Boy With Nonsyndromic Autism Spectrum Disorder


One UK reader did get Everolimus prescribed on the NHS, but that was because the child was diagnosed with a genetic disorder called TSC. Several readers of this blog have tried Rapamycin as used in the Chinese case study.

If you do not have an over activated immune system, Rapamycin will cause the problem of an underactive immune system.



 These genes all play a role in the immune system.

The human leukocyte antigen (HLA) system is a complex of genes in humans which encode cell-surface proteins responsible for regulation of the immune system.

The immune system uses the HLAs to differentiate self cells and non-self cells. Any cell displaying that person's HLA type belongs to that person and is therefore not an invader.


HLA Immune Function Genes in Autism

The human leukocyte antigen (HLA) genes on chromosome 6 are instrumental in many innate and adaptive immune responses. The HLA genes/haplotypes can also be involved in immune dysfunction and autoimmune diseases. It is now becoming apparent that many of the non-antigen-presenting HLA genes make significant contributions to autoimmune diseases. Interestingly, it has been reported that autism subjects often have associations with HLA genes/haplotypes, suggesting an underlying dysregulation of the immune system mediated by HLA genes. Genetic studies have only succeeded in identifying autism-causing genes in a small number of subjects suggesting that the genome has not been adequately interrogated. Close examination of the HLA region in autism has been relatively ignored, largely due to extraordinary genetic complexity. It is our proposition that genetic polymorphisms in the HLA region, especially in the non-antigen-presenting regions, may be important in the etiology of autism in certain subjects.

One specific HLA gene has been studied in autism.

 Inheritance of HLA-Cw7 Associated With Autism Spectrum Disorder (ASD)

Autism spectrum disorder (ASD) is a behaviorally defined disorder that is now thought to affect approximately 1 in 69 children in the United States. In most cases, the etiology is unknown, but several studies point to the interaction of genetic predisposition with environmental factors. The immune system is thought to have a causative role in ASD, and specific studies have implicated T lymphocytes, monocytes, natural killer (NK) cells, and certain cytokines. The human leukocyte antigen (HLA) system is involved in the underlying process for shaping an individual’s immune system, and specific HLA alleles are associated with specific diseases as risk factors. In this study, we determine whether a specific HLA allele was associated with ASD in a large cohort of patients with ASD. Identifying such an association could help in the identification of immune system components which may have a causative role in specific cohorts of patients with ASD who share similar specific clinical features. Specimens from 143 patients with ASD were analyzed with respect to race and ethnicity. Overall, HLA-Cw7 was present in a much greater frequency than expected in individuals with ASD as compared to the general population. Further, the cohort of patients who express HLA-Cw7 shares specific immune system/inflammatory clinical features including being more likely to have allergies, food intolerances, and chronic sinusitis as compared to those with ASD who did not express HLA-Cw7. HLA-Cw7 has a role in stimulating NK cells. Thus, this finding may indicate that chronic over-activation of NK cells may have a role in the manifestation of ASD in a cohort of patients with increased immune system/inflammatory features.


The therapeutic implication would be to look at immunomodulatory therapy.

At the simple level you have NSAIDs like Ibuprofen, but then you have the more potent drugs used to treat psoriasis, arthritis, IBD etc.

If you saw Dr Arthur Krigsman, the autism gastroenterologist, I guess he would prescribe Humira.  This is an injection you take every few weeks.  That very well might help your son in many ways. He does also come to Europe for consultations. You would need a colonoscopy.

Some British parents take their autistic kids with GI problems to Italy for treatment. You could ask the Thinking Autism charity who they go to see. One of these doctors presented at their conference in London in 2019.  He used some of Krigsman’s slides in his presentation.



Neuregulin 1 and 2 are implicated in brain disorders. NRG1 is well known as a schizophrenia gene, but it has been shown to be miss-expressed in autism as well.

NRG2 also plays a role in many neurological conditions.  

Neuregulins in Neurodegenerative Diseases 

The downstream effect of NRG1 is on epidermal growth factor (EGF). There are expensive cancer drugs like Lapatinib that are inhibitors of EGFR. 

As I have written in my blog, disturbed growth factors is a recurring feature of autism. This is why son many autism genes are also cancer genes. Don’t worry, this does not mean everyone with autism is going to get cancer.



Try and find a doctor who is interested to treat your son.

I think you will make great strides by treating the GI problems that you see every day.

I did meet an UK autism mother at that conference in London in 2019 who was told by her doctor that her son’s GI problems would not be treated in the UK and she should look abroad. She went to Italy and solved his problems.  It sounds so bizarre, I would not have believed it to be possible, had I not been talking directly to the mother.  I did talk to the Italian gastroenterologist at that same event.  Contact Thinking Autism and ask who was the Italian who presented in 2019.


  1. My son and I are heterozygous for the CACNA1S gene. We learned this in Dec. 2022 after whole genome sequencing and working with Dr. Richard Boles. We learned he has de novo mutations (RIF1 is the big one, an extremely rare mutation).

    The way this parent describes their son overlaps with my own 13 yo.

    My child is minimally conversational, overall happy, and very extroverted, but his "conversations" with most people are socially "inappropriate" (he walks up to people and says things like, "If you spell Josephine with a lower case J it is wrong" and doesn't understand that this is not how you meet a new person). He has severe palilalia (repeating phrases over and over to himself and others) and laughs with such intensity sometimes he turns bright red.

    He had digestive problems in the past, but most of those resolved by age 8. He has celiac disease (as does his father). He covers his eyes often and buries his face in couch cushions. His neck and jaw seem to always be tight. We’ve taken him to various doctors and no one has an explanation. An MRI is coming soon, but we cannot sedate him with certain anesthetics because of the CACNA1S gene, and this has complicated getting imaging.

    Language disappeared between 20-24 months and reappeared at 3 y 9 mo after we introduced Bh4. My son had his first grand mal seizure last month, and now the pediatric neurology is more focused on the CACNA1S gene, though it's a unique one (vs. a more common CACNA1A gene directly associated with epilepsy).

    Thank you for this write up, as it's giving me more insight into LDN and how it affected my son. We took him off it about 4 months ago, because he's been on it since he was 3 and we are doing a trial of taking him off long-time meds to see if he still needs them. Now I wonder if his seizure is somehow connected to removing LDN.

    1. Hello,

      Thanks for the comment.

      My son, Vik, age 6 with ASD, has a mutation on CACNA1G and I have been wondering about getting an appointment with Dr.Boles. Could you please tell us a bit more about your experience with Dr.Boles? Thanks..


    2. I've worked with Boles. Apart from helping you get the WGS, he does nothing else. He won't prescribe any medications. Most likely he will strongly recommend the mito supplements from his own Spectrum Needs company. He will also recommend other supplements like magnesium. Then he recommends to work with Dr.Rossignol/Dr.Frye who are his friends. Unfortunately for me working with him was a duplicate effort, as a local neurologist did some Invitae testing which is not exactly WGS, but captured the same gene mutation that came up in WGS by Dr.Boles.

    3. Janu,

      Thank you for the reply. Having done the extended autism panel recommended by one of the readers here, I am fairly satisfied that there is not much more to know about his genetics.

      We have previously consulted with Rossignol's clinic. We are currently consulting Dr. Kirill Shylapnikov on the suggestion of Tatjana Pes (another known commenter on this blog) and I feel like he does a more comprehensive job at evaluating and explaining his idea of treatment.

      We did start fluoxetine (prozac) 5mg each night for my son, Vik (age 6 with ASD) after seeing one of your previous comments and reading Goldberg's book. Its been about a month and I think there is a step change upwards overall in his improvement. Some of it could be natural progression, some of it could be effects of a previous treatment (like FMT done a couple of months ago), so its hard to ascribe causality to the SSRI use. But I can at least say there has been no ill effects observed so far. Hope this helps someone.


    4. Hi Anvesh,
      Have you followed the whole Goldberg protocol, or only the SSRI?

    5. Wow that's scary I have an appt with Boles coming up very soon hope we get some actionable advise

    6. Dadulon, I gave a talk a while back about using genetic testing as a tool to treat autism. The conclusion was that while it is perfectly possible, nobody is really doing it, because doctors do not "do" personalized medicine, they do cookie cutter medicine. That is where you wait a couple decades for clinical trials, rather than apply tailored problem solving to unique cases.

    7. @deathmetal124/ Anvesh
      Where did you get FMT done ?

    8. @mummydear We did use valtrex for a while (about 15 days) and then started the SSRI. He is on 6mg a day once at night. (as prescribed in the book - as many mg as the the age of the child). I have not seen any negatives is all I would say at this point.

      There is another boy of same age with autism in our community, who I know gets no medical intervention and very little therapy. But I have seen a lot of progress in him over time. So he is my 'control' so to speak, but to me he is proof that a lot of improvement just happens naturally with age. That 's why I hold back on saying that the medicine alone made a difference unless its immediatley obvious.

      @Gabana We did the FMT in Hyderabad, India at a small center called Resplice Reconnect Center. Their website seems to be down but I can provide contacts if you are interested.


    9. Thank you, Anvesh. I intend to try Goldberg's protocol myself as soon as I get as much information as possible about its side effects and interactions with the meds and supplements we are already doing. I bet that the protocol's rationale makes 100% sense only for a specific subtype of autism, but, apart from the few parents who can do extensive and constant testing, I doubt that there are many people who know exactly their child's subtype. That's why we can't presume anything or write off anything when it comes to personalising our children's treatments.

    10. @Anvesh. Thank you so much for your reply. I am actually from hyderabad,India. We live in UK. Pls share their(FMT clinic) contact details I dont see their website n location and what other therapies have you tried from them if you can put in detail pls.
      I am reading the book you or Janu mentioned. The Myth of Autism by Dr Goldberg.
      My child is 4.5 year old,mild ASD. From birth he has Eczema n from 2 years onwards we could see speech delay. Except NAC n citrizene(for eczema) we gave no other meds. By improving his diet n giving fish oil, vitamins we have seen lot of improvement.
      For speech ,learning about Gestalt Language Processing GLP, reading Natural Language Acquisition on the Autism Spectrum
      by Marge Blanc will help

    11. Also, it has been more than 3 months since we started 5mg Fluoxetine (prozac) for my 6 yr old son, Vik. We have seen fantastic improvements, especially in his play with other kids. Four months ago, it was very hard to coax him to go out of the house, but now we are finding it hard to bring him into the house because all he wants to do is play with the kids. I remember reading a comment on this blog from a mother who said her 8-year old son turned from being a quiet to loud kid after low dose Prozac. I do feel something similar has happened with my son too.

      Of course, we did a lot more this summer - FMT, removed tonsils, dichloroacetate (DCA) to help mito, IGG supplements, periodic ibuprofen when sick, short burst of anti virals (valtrex) and anti-parasites (mebendazole), new montessori school where they go easy on the kids etc.

      So, it could have been any of the above or just his gradual progress, but my gut feeling is that Fluoxetine had a role to play in his personality change.


      P.S - If you want to see my other comments about my son's progress, you can type "Anvesh" in Google.

    12. hi, so you used prozac every day? 5mg for 6y old kid ?

    13. Yes once a day at night. According to Goldberg, the dosage is as many mg as age of the child. So for our son it would be 6mg as he is 6 years old.


    14. Low dose Prozac is very interesting. The dose is high enough to increase Allopregnanolone, but not high enough to increase serotonin. If the good effect starts quickly you know the benefit is not via serotonin, because it takes a few weeks for Prozac to increase serotonin to its new higher level. The Allopregnenolone dose is suggested to be about 1/10 th of the standard dose of the drug. It then modulates GABAa receptors.

    15. Anvesh. how many kg does your child weigh?

    16. My son is around 20kg.



    18. There is a big variation in the dose given. Dr Goldberg has his own approach.

  2. Hi Peter,

    Since this post is about genes, I thought this would be a good spot to post this here. It's about a drug called Prazosin. I'm curious if anyone has used it here on this blog?

    Decreases marble-burying in mice.



  3. Thank you, Peter for all this information. It's a lot to take in. I'm sure I'll have further questions once I've gone through it all. So, I'll get back to you once I've put my thought in order.

  4. Thank you for your post Peter. As soon as I saw the email notification I read it.
    @Mummydear, last time you replied to me that you give DAO before meals to your son which helped me search about them. I read that EVOO extra virgin olive oil can also help. so when
    my 4 year old picky eater recently had constipation , gas and bloating, I started giving him daily 1 to 2 tsps of extra virgin olive oil and that seems to have helped. daily night time and morning soon after waking up.
    I think it will help others too.

    1. Thank you, that makes sense. We use EVOO + lemon juice mix in each of his savoury meals too, especially in soups. It does seems to help a bit with BMs, indeed. Fat digestion, though, seems to be quite problematic in our case, for which reason we never use fat or oils on their own and we had to abandon the keto diet for that reason too.

  5. Federico Balzola MD
    Division of Gastroenterology, University of Turin, Italy is the italian doctor presented in that event.


      Here's a video of him talking about GI symptoms

    2. Thank you so much for the information. I'm watching one of his presentations right now.

  6. Peter, thank you so much for your suggestions. We'll most probably have to travel to Italy to see Dr. Balzola. We recently travelled to do extra sequencing for the PIK3R1 gene, testing both of us, parents, in the process, and it results that it's not the SHORT syndrome, as the geneticist suspected, although my son is, indeed, very short and thin for his age. We worked with Dr. A. from Italy in the past, who prescribed Folinic Acid for speech (it didn't work), Glialia and the SIBO-C antibiotic/antifungal protocol, plus Itraconazole and Memantine, which had positive effects in terms of reversing the bloating and focusing his attention. We still cycle these meds when the symptoms resurface. Memantine's effect seems to fade away if used for long periods of time, so we cycle that too. We trialled also a low dose of Sirolimus a while ago, but had to stop it after two weeks because of mouth ulcers. Also, its effects, if any, were too subtle to be noticed. I might try it again, but along with Azithromycin this time, as one of your readers was suggesting. Ribavirin is also on my list to address the EIF4EBP1 gene; what holds me back is that I need to research more about the safety of the drug and, also, to be somehow sure that what I need to do is actually to inhibit, not to activate the expression of this gene (I am still learning to be able to distinguish a gain of function from a loss of function mutation). Coming from a family quite badly affected by arthritis, vasculitis and gut issues, I also realised that I can't dismiss the MIA model of autism in customising my son's treatments, although I didn't notice anything significant after a Minocycline trial, which is said to reverse autism in the corresponding mouse model. My son seems to respond very well to macrolide antibiotics, instead, which somehow makes sense, given that, sometimes, Dr. Michael Goldberg recommends Erythromycin to his patients for immunomodulation. I have had my son on sodium butyrate and tributyrin for a few years now, also on NAC, which seems to help, especially with his OCD and sleep. But, looking at the big players that made a visible difference to his cognition and OCD so far, Naltrexone and Azithromycin, I incline to think that the work on the opioid/dopamine pathways and the immunomodulation might be key factors in improving his condition. The fact that he also has severe chewing and swallowing problems, is still on pureed food and has extremely hypermobile joints suggests he might have EDS and an associated form of eosinophilic esophagitis and, possibly, gastroenteritis, which might be the root causes of his ongoing digestive issues and, indeed, inflammatory cytokines. Either way, having all these small insights and improvements along the way, be them even on/off improvements, still did not advance his cognitive status to the point where he would start to speak and communicate with us. My current big quest, therefore, is to find what you call "the game changer", or a polypill, highly personalised to his profile and needs. It might lie in grouping together drugs that work on the same pathway and make each other more potent. Or/and in drugs used counterintuitively but whose secondary ways of action hit the required targets. There is still a lot of thought and reading to be put into treatments we haven't tried yet, such as other ion channel blockers, Metformin, the Goldberg protocol (SSRI+Antiviral+antifungal meds), SSRI alone at a very low dose, PDE4 inhibitors, mGLUr5 inhibitors or, as a matter of fact, Suramin (when available), which is supposed to work well in the MIA model. I do hope that, in the end, my son's game changer will make itself apparent. Your blog has been an eye opener and a motivator to keep me looking for it. Thank you again, Peter.

    1. Hi, if Naltrexone and Azithromycin works you should try Naltrexone and vancomycin instead. It's example #4 in this patent document.


    2. That sounds interesting and promising, I will have a look into it. Thank you, Stephen.

    3. Probably why naltrexone works.


    4. Thank you, Stephen, for the link. I discovered in the meanwhile this article
      It is a case report about what they call "high opioid tone autism type", in which Naltrexone seems to have reversed the person's autistic behaviours. This type is characterised, amongst other features, by high pain threshold, which is definitely what my son has been always dealing with. One thing that is mentioned in the article is that high opioid tone may turn on inflammatory cytokines that disrupt gut function. It is a very interesting perspective on what might be going on in the case of the ASD kids who are always excessively happy, laugh inappropriately but are crippled with bad gut and neuroinflammation.

  7. We got WGS for our son. He was showing a very rare mutation on GABRB2. While not much research or knowledge exists about this mutation, there is a FB group of small number of impacted people from all over the world. In that FB group, many children are severely impacted with being bound in wheel chair, dependent on feeding tubes and having treatment resistant seizures. There is a small team of researchers currently working on this mutation with the parent driven efforts. While I realize my son's susceptibility to lose his walking ability can be correlated to this gene mutation, what I've found out is that you don't have to wait for decades for the researchers to come up with a solution. My son responds to anti-inflammatory treatments and is now able to walk like a normal child. He could have been wheel chair bound with a bad prognosis, if we had done the genetic testing very early as we would have been told there is no treatment for this. I'm so glad we did the genetic testing late, after we figured out what helps.

    1. Good point Janu. I recall a mother who made huge efforts to get her daughter to speak. Later on, she did genetic testing and that showed a mutation that would cause the person to be non-verbal. Had she been told about the gene at the outset, she might have given up trying to teach speech.

    2. Hi Janu, can you please share the details of genetic testing you have done and country, we would like to do it.

    3. Sudhakar, I got the Invitae test done in USA from a local neurologist. I also got the WGS done from Dr.Boles who also is in USA. From both doctors I did not get any actionable treatments based on the genetic results. I might sound very opinionated. But I'll say it anyways. Genetic testing will not take you anywhere. It's okay to get it, just for information, if it's possible. Even though my son's particular disability can be correlated to that genetic mutation, he responds to immune controlling treatments. I think genetic mutations are side effects. They are not the cause.

  8. Hi Peter,

    We recently found out my daughter has a WASF-1 mutation. They said this mutation is not usually associated with ASD but is associated with a newly discovered rare condition in which the carrier is non verbal and has seizures. (Insert confused face emoji)

    1. Diseases associated with WASF1 include:

      "Neurodevelopmental disorder with absent language and variable seizures and non-specific syndromic intellectual disability."

      There are 3 specific mutations listed, which all have a similar clinical picture.


      Intellectual disability
      Neurodevelopmental disorder with absent language and variable seizures


      Intellectual disability
      Neurodevelopmental disorder with absent language and variable seizures.
      Epileptic encephalopathy


      Intellectual disability
      Neurodevelopmental disorder with absent language and variable seizures

      Another summary does use the autism word:-

      Neurodevelopmental disorder with absent language and variable seizures: A disorder characterized by neurodevelopmental abnormalities, including moderate to profound intellectual disability, with autistic features, seizures, severe impairments in speech, and gross motor delay.

      It looks pretty clear that a mutation of WASF-1 might well lead to an autism diagnosis. The word "autism" is just an observational diagnosis and it is much easier nowadays for the clinician to diagnose it as autism, rather than intellectual disability.

      It is not so newly discovered; they are already publishing case studies on it. This is from 5 years ago:-

      De Novo Truncating Mutations in WASF1 Cause Intellectual Disability with Seizures

    2. There is a gene therapy, called OTL-103, in trials for the related Wiskott–Aldrich syndrome.

      WASP-1 = Wiskott-Aldrich syndrome protein 1

      This gene is on the X chromosome. Boys have one, but girls have 2. Your daughter should have 1 functional copy.

      So a girl would likely have only 1 mutated copy and as a result be less affected than a boy.

      The same is true with the better-known Fragile X syndrome. In twins with Fragile X, the boy is severely affected while his twin sister is much more functional.

  9. Hello Peter, I'm currently waiting on the results from my son's Autism screening. He is turning two. First let me thank you for this resource. My son has a compound heterozygous c677t and a1298c MTHFR polymorphism, so I'm hopeful folinic acid will help his condition. Any advice would be appreciated.

    To my question, has anyone tried Idebenone in the treatment of Autism? I only know of this medication due to a friend with leber's hereditary optic neuropathy (LHON).

    1. These are very common mutations and are unlikely to cause autism.

      What is an MTHFR mutation?

      “MTHFR mutations do not require medical treatment. That said, making dietary and lifestyle changes can often help offset any resulting nutritional deficiencies.
      For example, people with high homocysteine levels due to folate or vitamin B12 deficiencies can take folic acid or vitamin B12, respectively.
      Methylenetetrahydrofolate reductase (MTHFR) is an enzyme that breaks down the amino acid homocysteine. If the MTHFR gene that codes for this enzyme mutates, it may contribute to a variety of health conditions ranging from depression to some cancers.
      People have two MTHFR genes, inheriting one from each of their parents. Mutations can affect one (heterozygous) or both (homozygous) of these genes.
      There are two common types, or variants, of MTHFR mutations: C677T and A1298C.
      These gene mutations are relatively common. In fact, in the United States, around 25% of people of Hispanic descent and 10–15% of people of Caucasian descent have two copies of C677T.”

      If you are concerned, ask your doctor to test for folate and vitamin B12. If your son has low levels then you can supplement them.

    2. Idebenone (known as Catena, Raxone, Sovrima etc) works as a transporter in the electron transport chain of mitochondria and thus increases the production of ATP (adenosine triphosphate) which is the main energy source for cells.
      It would potentially benefit people with impaired mitochondrial function.

      Not surprisingly, it has been considered for use as a cognitive enhancer in older people.

      Will it work for some autism? Quite possibly, but unlikely the ones who are hyperactive.

    3. I'm curious to your opinion on this study. "Prenatal Exposure to Maternal Depressed Mood and the MTHFR C677T Variant Affect SLC6A4 Methylation in Infants at Birth"

    4. This confirms the known association between C677T and depression. It is telling us which serotonin receptor is affected. Not surprisingly there is an affect on the infant born to a depressed mother. The mechanism is epigenetic, as are many environmental factors that influence offspring - everything from pesticides to recreational drug use by parents.

  10. So, to follow on - met with Dr. Boles. WGS did not reveal anything more than the WES from years ago; namely the ANK3 mutation which *might* be responsive to Lithium at naturopathic or perhaps pharmacological doses.. lithium might "rescue dendritic abnormalities" in mice in vivo. So, onto the Lithium trial. Also NDMA agonists to glutamate receptors, like memantine and amantadine were suggested. Any thoughts and comments on this are appreciated

  11. A study for you Peter in case you haven't seen it:
    Defining blood-induced microglia functions in neurodegeneration through multiomic profiling.

    "Deletion of the blood coagulation factor fibrinogen largely reversed blood-induced microglia neurodegenerative signatures. Genetic elimination of the fibrinogen-binding motif to CD11b in Alzheimer’s disease mice reduced microglial lipid metabolism and neurodegenerative signatures that were shared with autoimmune-driven neuroinflammation in multiple sclerosis mice."


  12. Peter, do you know of any commercially available cytokine kits?

    I love how the Chinese have been using cytokine assays in there ASD research. For example, I guess IL-8 is elevated in both the parents and children with ASD.


    1. Stephen, I have not looked beyond tests available at local labs.

    2. Peter, thank you for the response. Yeah, the only way I've come across cytokines tests are through academic research studies.

    3. Another area I've been focusing on is Vascular Growth Factor.

      Bumetanide decreases it and I guess its elevated in ASD children.

  13. A lot of people in our community locally are doing wes via a chinese company called Bgi. Due to different legal systems it is possible via BGI to get an excel file with things that are ‘outside of the normal stuff’ but either of unknown significance or related to enhances risks for issues that arrive later in life. This is not possible in Europe or the US.
    People from our community send me these files in a ‘whats your take on this’ way. I always will say that I have no clue about genetics. I just don’t understand any of it.
    BUT, I will say that of the kids I have seen files on, all have about 10 of the same ‘unknown or insignificant’ changes in that excel file. And these changes are related to mucosa and mitochondria. Though the children are sort of from the same region they are several generations back from very different parts of the region, so any genetic ‘common heritage’ would have to be more than a 100y or even 200y ago.
    There is the theory of ‘multiple hits’ in genetics - basically having a weak spot and then the enviromental factors do the job. Many people think of the connection between genetics and autism in those terms and that is my opinion too.
    It always helps when you have an interesting find that can lead to personalized therapy.
    I personally was quite disappointed. We have variants kn the Gnai1 and Rhobtb2 gene. The described syndromes are as far away from my child as a sprained ankle from an amputated leg - she is not remotely that severe and lacke many symptoms. We did nit gain any insight into therapy modes and even thoufh there is a child registered in Switzerland with the exact same Rhobtb2 variant and ‘developmental problems’ we have been unable to reach that family.
    So overall…for most, genetics is nit the answer.

  14. Hi Tatanja,

    I can’t find the exact study, but I do remember it from a newspaper article. An Australian study that suggested that all genetics are in fact epigenetic and that even the most extreme genetic diseases have environmental conditions that must be met for the condition to occur.

    If confirmed this would go a long way to explaining Autism.

  15. Hi Peter. What tests would you recommend for cerebral folate deficiency (non-invasive tests I mean). My brother has ASD and had violent tantrums before introducing folinic acid. Folinic acid has completely stopped the violent outbursts, and he is able to deal with disappointments and change of plans much more easily. Language has improved somewhat, and he tries to make new sentences with what he already knows. It's very exciting, and I would like to try leucovorin, but doctors are not willing to even listen without evidence.

    1. There is a blood test:-

      Leucovorin is calcium folinate, which effectively is folinic acid.

      Dr Frye has published ample research to show that a sub set of autism does respond well to calcium folinate (leucovorin). Just Google it and show it to the doctor..


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