New mutations implicated in half of autism cases

news@nature.com ^ | 24 July 2007 | Heidi Ledford

[neverdem]

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Published online: 24 July 2007; | doi:10.1038/news070723-1

New mutations implicated in half of autism cases

Disorder linked to genetic differences between parent and offspring.

Heidi Ledford

Autistic children display a wide range of different symptoms.HENNY ALLIS / SCIENCE PHOTO LIBRARY

Half of all cases of male autism may be caused by spontaneous genetic mutations, say researchers who have studied the genetic patterns of the condition. Offspring who inherit such mutations are at a greater risk of having an autistic child themselves.

Autistic people have difficulty relating socially with others and tend to focus obsessively on a narrow set of interests. Three to six out of every 1,000 people are expected to have the condition; its cause is unknown but there is thought to be a strong genetic component.

"That genetics plays a major role in autism has been obvious now for 20 years or more," says Isabelle Rapin, a neurologist at Albert Einstein College of Medicine in New York, who was not affiliated with the study. "The evidence for genetics is not controversial."

But determining how genes affect autism has been difficult. Autism is a complex disease with a wide range of symptoms and severity. It also affects four times more males than females, for unknown reasons.

Spontaneous mutation

Earlier this year, a genome-wide scan linked some cases of autism with mutations in the number of copies of certain genes. Ten per cent of autistic patients had copy-number mutations that were not present in either parent, showing that the mutations were spontaneous¹.

But Michael Wigler, a geneticist at Cold Spring Harbor Laboratory in New York and a lead author on the study, says that the study probably missed some copy-number mutations. "We were sure that 10% was an underestimate," he says.

So Wigler and his colleagues turned to a database containing pedigrees of families with two or more autistic children and asked: if the family's first two children were autistic, what were the chances that the third was autistic as well?

In 86 families with two autistic children and a third, male child, 42 of the third-born children showed autistic symptoms, the researchers report in Proceedings of the National Academies of Sciences².

This suggests that parents had a one-in-two chance of passing on a mutation to their offspring, matching a dominant inheritance pattern. Another database gave the same result.

Handed down

Using mathematical models, Wigler's team found that the simplest way to describe the patterns of autism inheritance was to divide parents into two risk classes: those who carry a pre-existing autism-causing mutation, and those who do not.

The models suggest that about half of autistic children are born to parents with no previous genetic predisposition to autism, suggesting that the cases are caused by spontaneous mutations.

Older mothers, who are more likely to have autistic children, could fall into this class, notes Wigler. Such mothers' eggs have had more time to accumulate mutations.

Once those spontaneous mutations have been passed on, the offspring — particularly women, who can carry the mutation without showing symptoms — have a high risk of having an autistic child. Males with the mutation would also bear this risk, but are also likely to be autistic and therefore less likely to have children.

The researchers' model suggested that about a quarter of autistic children have inherited a copy-number mutation from their parents.

"It's a new way of looking at the data," says Rapin. Future studies using data from other family members are needed to further test the new models, she says. Other factors, such as complications during pregnancy, and the influence of multiple genes, may also be important in causing autism.

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References

1. Sebat, J. et al. Science 316, 445-449 (2007). | Article | PubMed | ISI | ChemPort |
2. Zhao, X. et al. Proc. Natl Acad. Sci. USA doi: 10.1073/pnas.0705803104 (2007).

[Chickensoup]

Personally I think it is something as simple as the widespread use of plastics in our food supply. I know they are supposed to be bio-inert. But they really are not over time.

[CJ Wolf]

Radiation from the color spectrum of purple emitted and received into the body from sitting too close to the TV watching Barney. That's my guess. But it might be the center of green surrounded by purple. I need more funding to research this.

[madison10]

What’s tweaking our DNA to mutate?

Icky food and toys from China.

[edsheppa]

Ten per cent of autistic patients had copy-number mutations that were not present in either parent, showing that the mutations were spontaneous.

What if 10% of all children have copy-number mutations that are not present in either parent?

[hunter112]

What’s tweeking our DNA to mutate?

Clearly, in the industrial age, we're exposed to all kinds of chemical compounds that people a couple of centuries ago could never have encountered. Also, things that would formerly kill babies either in utero, or shortly after birth, are being "corrected" for, and the genetic underpinnings of those things are being passed on to the next generation.

[neverdem]

Thanks for the link.

[SunkenCiv]

Except when driving... then, everyone falls into three groups — Me, those who are driving too slow, and those who are driving too fast. ;’)

[ken21]

thanks.

i know an autistic child.

[SunkenCiv]

We don’t have to worry about this much longer — cases after January 1, 2010, will be referred to as “teenism”.

[Hot Tabasco]

i know an autistic child.

I am highly suspicious of my nephew's 4 year old son and the younger sister. I have talked to one of my sister's about the child's behavior and she agrees that there is something wrong. However, she says that when she talks to our other sister about her grandson, she says that the childs mother will not enter into any discussion about it. Its almost as if the mother is in denial that there may be a problem with the son and quite possibly the younger daughter too......

[Monkey Face]

Ohyah...I forgot about that! LOL!

[Zechariah_8_13]

It seems like everyone here on FR thinks Big Pharma can do no wrong, and wants to say that vaccines have nothing to do with autism — but I know several families whose children were perfectly normal, received a vax, and they then watched their normal child regress into autistic behaviors nearly immediately.

When you overstimulate the immune system (i.e. with vaxes) you can’t possibly predict every outcome. I believe some children are just more susceptible.

[ken21]

that’s sad.

this girl is 4 years. she’s the daughter of a friend of mine. my unprofessional opinion is that she’s a “high functioning” autistic child.

when i first met her she was 3. now, she’s picking up language at an accelerated rate.

her autism includes: 1. she doesn’t recognize emotions in other people. for example, if her mother gets angry at another person, she doesn’t see it.

2. she’s very visual. very, very. likes puzzles. draws well.

3. she has no fear of strangers. this requires complete supervision of her.

she likes men. very few men she does not like. most children her age are removed from strangers and men.

she adores her princess videos, dolls, etc. she stares at her princess and mermaid dolls for hours.

[Zechariah_8_13]

What I’m saying:

Genetics loads the gun, but environment pulls the trigger.

[neverdem]

Genetics loads the gun, but environment pulls the trigger.

That's a common hypothesis. IMHO, this latest stuff implicates copy number variation, and more specifically, IIRC, the deletion of genes in males. I'm not a geneticist, just a physician trying to understand what's going on.

IMHO, I think the increased prevalence of autistic spectrum disorder is due to having more specific diagnostic criteria, i.e. in the past many would have been diagnosed as mentally retarded, in addition to those now diagnosed with pervasive developmental disorder and Asperger's syndrome.

[Hot Tabasco]

My nephew’s son is not loveable like the other kids in the family, does not interact with adults other than his parents,and the most telling of all is he will suddenly stop what he is doing and start shaking his hands until his mom has to go over to him and stop him. I even saw this last Christmas when he was seated at the childrens table for dinner. He stopped eating and started shaking his hands till his mom stopped him and had him refocus on his meal.

[Incorrigible]

Those are some telltale signs there.

Your sister is doing him no favors by denying that he has Autistic behaviors. The earlier the intervention, the better it will be for him in the long run.

[Incorrigible]

the increased prevalence of autistic spectrum disorder is due to having more specific diagnostic criteria

That's definitely happening and yes, they would would have been classified as mentally retarded in the past.  Also the broadening of the Autism spectrum by Autism advocate organizations (something I don't agree with).

However, there have been studies done that indicate that the rise is not entirely from better diagnosis.

 

[nmh]

Genetics COULD play a part but they really can’t predict it.

A couple we know had one autistic child. They did a genetic work up and saw the odds as astronomical that the next would be autistic. The plan was that the second child would care for the older brother. Well, against all odds, the second son was also autistic.

[nmh]

You’re right.

They really don’t know.

They’d like you to believe they are making progress in udnerstand this but they haven’t made any progress.