Gene causes retardation in Down syndrome: study

WASHINGTON (Reuters) – A gene mutation that shrivels brain
cells may be responsible for the mental retardation seen in
Down syndrome, U.S. researchers reported on Wednesday.

The finding suggests there may be a way to interfere with
or even reverse the mental decline often seen as people with
Down syndrome get older. The finding, published in the journal
Neuron, also may apply to Alzheimer’s disease, the researchers
said.

“If we can decrease the expression of this gene we may be
able to provide something more than supportive care to people
with Down syndrome,” said neurologist Dr. William Mobley of the
Stanford University School of Medicine and Lucile Packard
Children’s Hospital in California.

Reducing gene expression turns down the activity of a gene.

Down syndrome is the most frequent genetic cause of mental
retardation and affects one out of 800 babies born. It is
caused when people have an extra copy of chromosome 21, making
three instead of two.

It causes early learning difficulties, sometimes causes
childhood heart disease and leukemia. Most people with Down
syndrome develop Alzheimer’s disease by the age of 40.

The researchers worked with genetically engineered mice to
find the gene, which is called App — short for amyloid
precursor protein. Mutations are known to cause early-onset
Alzheimer’s disease in otherwise healthy people.

Like people with Down, the mice had three abnormal copies
of the App gene. When the researchers deleted the third copy of
App in the mice, the animals became more normal.

“We’re now investigating ways in which we might be able to
turn down App expression,” Mobley said in a statement.

“It’s not even necessary to turn it off completely. All we
need to do is to reduce it by one-third, from 150 percent of
normal back down to 100 percent,” said Dr.Ahmad Salehi, who led
the study.

The researchers stressed that deleting the third copy of
App did not restore the mice to normal, so other genes must
also affect the brain decline.

“First we need to figure out at a molecular level how App
works in Down syndrome,” Mobley said. “Then we need to examine
other genes that might be involved and test possible compounds
in mouse and human cells. If we are able to do all that, we
might begin to think of helping children and adults with Down
syndrome to develop and age more normally.”