Comments on: Disruptions in Contactin 4 and Autism

By: In Search of Another Hidden Horde, Autistic Children with Mito?

In Search of Another Hidden Horde, Autistic Children with Mito? — Mon, 28 Apr 2008 19:00:45 +0000

[...] link autism to mercury. Concurrently, a number of studies offer further evidence about genetic of factors and autism. Also at the same time, proponents of the view that some external, environmental factor [...]

By: fiona

fiona — Sat, 29 Mar 2008 21:36:44 +0000

I am not a scientist, but apropos fathers of children with diagnosis of autism not appearing to ‘have’ autism themselves, is this not a cultural factor, that is mildly ‘autistic’ features in the past have been accepted as ‘eccentricity’ or the features of ‘a typical man’ and therefore not ‘pathologised’. Moreover, with foregrounding of feminist perspectives in relationships and educational issues (the desire that men are ‘empathic’) are there really more men and boys with autism around, or has our 21st century culture just highlighted what was, in its mildest form, ‘maleness’?
As for one of my sons, there is no doubt whatsoever. He is severely autistic, with limited speech and language. But beautiful, nonetheless.
Fiona

By: Regan

Regan — Thu, 20 Mar 2008 13:46:20 +0000

MR is a determination from a formal instrument, and seems to have some dependency on what instrument is used and what is being measured, and when. Behaviors may be retarded relative to some stated criterion, not people.
Autism is a diagnosis based on observation, and in re: educational classification seems to be dependent on variables outside of phenotype anyway.
To me, both of those are labels and subject to definition change more easily than biology.
I have no issue with the genetic studies and am not looking for whether there is some “product based” application coming out immediately. Basic research contributes to identifying the mechanisms that relate to phenotype.

Emily, thanks for your comments.

By: Emily

Emily — Thu, 20 Mar 2008 13:29:13 +0000

Dopamine misfiring underlies a laundry list of disorders. That doesn’t mean that somehow, dopamine misfiring isn’t related to each and every one of those disorders, and it doesn’t mean that a person with one disorder related to dopamine misfiring must also have all or any of the others.

And considering the involvement of the brain and neuronal communication in autism and in intellectual disability, I would actually expect that there would be a mechanism or mechanisms in common, especially related to short-term memory issues. But…genes are often quite long, thousands of bases long. Mutations in one part of a gene can result in a related phenotype that is entirely different from what results from a mutation in another part of the *same* gene. Thus, it doesn’t really matter in the context of this discussion that MR is linked to the same gene that the authors purport to link to autism *unless* the mutations identified in each study are identical.

By: RAJ

RAJ — Thu, 20 Mar 2008 11:20:06 +0000

Ahain, contactin genetic anomalies are not specific to autism:

http://www.ncbi.nlm.nih.gov/pubmed/16571880?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

The phenotype for this anomaly is mental retardation, not autism. Mentally rearded people share non autism specific isolated features that have been descried by Kanner as quai-autism, as has Romanian orphans who were subjected to early institutionalized emotional deprivation.

By: Kristina Chew, PhD

Kristina Chew, PhD — Thu, 20 Mar 2008 04:37:26 +0000

Thanks, Emily—I was also thinking about Wigler’s study on de novo mutations in regard to this latest study (and I think Hatchwell might have some affiliation to the Cold Spring Harbor lab where Wigler is?). I just see so many similarities between Jim and Charlie, and Charlie and me. We have different “differences,” but plenty of similarities.

By: Emily

Emily — Thu, 20 Mar 2008 01:53:39 +0000

” If the father has the same genetic anomaly and the father does not have autism what evidence do we have that the genetic anomaly causes autism? None. Reports like this come out at a pretty steady rate. I think it has more to do with gentic researchers trying to hang on to their grants, and medical reporters who would gladly reiterate “2+2=5″ if the person who told them that had an authoritative association.”
It’s called “incomplete penetrance,” and I can think of, off of the top of my head, five mechanisms by which a father might not manifest symptoms but the child does not, or vice versa.

There are many examples of a parent and a child carrying the same mutations but of only the child’s manifesting symptoms. Fragile X and Huntington’s come to mind, although they are trinucleotide expansion diseases. The authors make reference to “copy number variation” in the context of the mutation, and that may be relevant, although I did not see clarification of that in my quick scan of the paper.

Anyway, the quick, off-the-top-of-my-head ways that dad could carry the mutation but not have the disorder, while child has it, are…
1. Epigenetic regulation differs between father and child. This is what makes even identical twins different in some ways, in spite of their identical genomes.
2. There are transcriptional mechanisms that influence the activity of the gene.
3. There are post-transcriptional/pretranslational mechanisms under regulation that may vary from individual to individual.
4. There are posttranslational modifications that vary from individual to individual, even with an identical gene sequence that produces an identical protein,.
5. There is a multifactorial influence that affects the level to which the pathology is manifested.

I can see why a reporter wouldn’t want to get into that.

The authors discuss this in their paper, which is open access, so anyone can read it. They provide their rationale for finding this particular mutation linked to autism. They also discuss examples of families where one manifestation of the disease appears to have a heritable mutation link, but the other manifestation seems to be de novo or arises via a completely different mechanism.

By: Kristina Chew, PhD

Kristina Chew, PhD — Wed, 19 Mar 2008 23:01:02 +0000

I found the observations about a father with ADHD or Asperger's (and my husband has some Aspergerish-like traits and definitely ADHD; he would have had an IEP now) passing on the mutation to a child who then has autism of interest; the study also mentions the recent research by Michael Wigler on spontaneous vs. heritable autism.

By: John Gilmore

John Gilmore — Wed, 19 Mar 2008 22:23:50 +0000

Here we have yet another example of autism reporting where obvious questions are not asked: If the father has the same genetic anomaly and the father does not have autism what evidence do we have that the genetic anomaly causes autism? None. Reports like this come out at a pretty steady rate. I think it has more to do with gentic researchers trying to hang on to their grants, and medical reporters who would gladly reiterate “2+2=5″ if the person who told them that had an authoritative association.

By: Jill

Jill — Wed, 19 Mar 2008 21:00:24 +0000

After reading the whole article, I am a little ticked off at what Hatchwell said regarding parents are more likely seek the diagnosis of autism for kids that have mild learning problems. My kids do not have a mild learning problem. I do not know if there is an epidemic or not but I do know that my kids have very little chance of living an independent life. My county MRDD went from 2,000 adults/children looking for services to over 15,000 in just ten years.

I am still not understanding why the father can have this mutation and not be affected but yet the child is. Does the child have other mutated genes?