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Gene Expression Profile Distinctions In Autistic Children Identified

Genomic analysis could add biological certainty to behavioral diagnosis

A group of genes with known links to natural-killer cells --

the first to attack viruses, bacteria and malignancies -- are

expressed at high levels in the blood of children with autism when

compared to children without the disorder, according to a new study

from the UC M.I.N.D. Institute. Researchers also found gene

expression distinctions in children with early onset and regressive

forms of the disorder. The outcomes, published in the January issue

of Genomics, offer hope that gene expression analyses can provide

biological evidence of autism, currently diagnosed only through

behavioral assessments, in some children.

"What we found were 11 specific genes with expression levels

that were significantly higher in the blood of children with autism

when compared to the blood of typically developing children," said

Sharp, senior author of the study and professor of neurology

with the M.I.N.D. Institute.

"Those 11 genes are all known to be expressed by natural-killer

cells, which are cells in the immune system necessary for mounting a

defense against infected cells. We were surprised by our results

because we were not looking for these particular genes. And while a

number of studies have shown immune system dysregulation to be an

important factor in autism, ours is one of the first to implicate

these particular cells."

In conducting the study, Sharp, molecular pathologist Jeff

Gregg and their M.I.N.D. Institute colleagues used blood samples from

35 children diagnosed with autism, 14 with development delay but not

autism and 12 typically developing children. The samples were

subjected to gene expression analysis using microarrays and compared

for common patterns. In addition to finding the 11 genes with natural-

killer cell connections shared by all of the children with autism,

they identified a pattern of 140 genes differentially expressed in

children with the early onset form of the disorder and a pattern of

20 genes differentially expressed in children with the regressive

form of the disorder. The team is the first to use genomic profiling

of blood to observe differences in children with autism.

A serious and increasingly prevalent neurodevelopmental

disorder, autism is characterized by language impairments, social

deficits and limited, repetitive behaviors. While some parents report

they knew something was wrong with their child close to birth, others

report their children progressed just like others and then lost

social and/or language skills later, usually between the ages of 1

and 2.

These separate experiences led clinicians to hypothesize that

there are at least two types of autism -- early onset and regressive.

This study offers biological evidence of those two subtypes.

Microarrays are used to examine the expression levels of

thousands of genes simultaneously. Because of its accuracy, the

technology may become an important diagnostic tool for a variety of

neurological conditions, including ischemic stroke and multiple

sclerosis. To perform the analysis, RNA is isolated from cells in the

blood. Complimentary strands of DNA (cDNA) are then created using the

RNA as a template. Fluorescently labeled cRNA is next made from the

cDNA and hybridized with the DNA on the array.

Scanners using laser technology then read the array, revealing

which genes are expressed and at what levels.

In addition to being expressed by natural-killer cells, some of

the 11 genes found to be expressed at higher levels in children with

autism are also expressed by CD8+ T lymphocytes -- cells that target

infected cells and, once bound to them, destroy them. It is not yet

clear whether autism involves a primary problem in natural-killer

cells, CD8+ lymphocytes or both.

"What we are seeing can reflect something in the environment

that is triggering the activation of these genes or something genetic

that the children have from the time they were conceived," Sharp

explained. "Such an immune response could be caused by exposure to a

virus, another infectious agent or even a toxin. Another possibility

is that these changes represent a genetic susceptibility factor that

predisposes children to autism when they are exposed to some

environmental factor."

He added that the current study also does not identify whether

or not the natural-killer cells are functioning abnormally, which

further work by M.I.N.D. Institute immunologists will reveal.

"If the natural-killer cells are dysfunctional, this might mean

that they cannot rid a pregnant mother, fetus or newborn of an

infection, which could contribute to autism."

Gregg and Sharp consider the findings preliminary until they

can be replicated, but still believe the study results point them in

a new research direction that will shed light on the biological

foundations of autism and eventually lead to new therapeutic targets.

The study, "Gene Expression Profiles in Children with Autism,"

was funded by the National Institutes of Environmental Health

Sciences and the U.S. Environmental Protection Agency through the UC

Center for Children's Environmental Health and the UC

M.I.N.D. Institute. A copy can be downloaded at www.sciencedirect.com.

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--- End forwarded message ---

Happel's wrote:

thryoid function was one of the

first things our doctor looked into so as far as i'm concerned, you're

right on.

-----

Original Message -----

From:

littlelief

To:

miralax

Sent:

Sunday, January 27, 2008 7:37 PM

Subject:

one other thought - thyroid function

Reading more at the enzymes in autism groups' file reminded me

about

checking the thyroid function. Our new doc did blood work up

(including thyroid markers) and did mention that it's important to

check thyroid function in constipated kids.

There is a lot of thyroid function information at the vitamin K

protocol Yahoo group.

Not sure if this will help anyone, but in searching to figure out why

my son is constipated, I'm looking for any and all info!

best,