Gene for brain connections linked with autism

WASHINGTON (Reuters) - A gene that helps the brain make connections may underlie a significant number of autism cases, researchers in the United States reported on Tuesday.

Neuron activity in the brain in an undated illustration. A gene that helps the brain make connections may underlie a significant number of autism cases, researchers in the United States reported on Tuesday. REUTERS/NIGS/Kim Hager/University of California, Los Angeles/Handout

Disruptions in the gene, called contactin 4, stop the gene from working properly and appear to stop the brain from making proper networks, the researchers reported in the Journal of Medical Genetics.

These disruptions, in which the child has either three copies of the gene or just one copy when two copies is normal, could account for up to 2.5 percent of autism cases, said Dr. Eli Hatchwell of Stony Brook University Medical Center in New York, who led the study.

“That is a significant number,” said Hatchwell.

“Generally the mistake that people make is they are looking for one unifying cause for autism, and there is no such thing and there never will be,” Hatchwell said in a telephone interview.

He said his finding adds to the list of potential tests for autism, and perhaps treatments for a range of conditions known as autism spectrum disorders.

Hatchwell’s team tested 92 patients from 81 families with autism spectrum disorder and compared them to 560 people without autism.

They did a whole genome analysis, looking at the entire DNA map, and found three of the patients had deletions or duplications of DNA that disrupted contactin 4.

They were all inherited from fathers without a history of autism, which can cause severe social and developmental delays and even mental retardation.

This may seem like a small number but millions of people have some type of autism, Hatchwell noted. The U.S. Centers for Disease Control and Prevention estimates that 1 in every 150 children has autism or a related disorder such as Asperger’s syndrome, which is marked by often mild social awkwardness.

“Autism is a syndrome. These individuals have all been grouped together as having the same thing. There will be many, many dozens if not hundreds of different causes,” he said.


Contactin 4 is involved in the development of axons, which are the long strings that connect one neuron to another. Other

disruptions of this gene are known to cause developmental delay and mental retardation.

The genetic mutation is present at birth, Hatchwell said.

“In each case a father who was reported as normal had the same thing,” he added.

“This happens in genetics all the time. Often there are cases in which someone is reported as normal. They pass it on to their child, who has severe disease.”

It could be the fathers had mild Asperger’s or some other condition that was never diagnosed when they were children. Hatchwell noted that parents today in the United States are far more likely to seek a diagnosis for autism spectrum disorder in their children than parents were in past generations.

This is controversial, with some advocates and experts saying autism and related disorders have become more common in recent years, and others saying there is no evidence this has occurred.

“My personal view is that it is not becoming more prevalent,” said Hatchwell. “If a parent has a child with some sort of learning problem, if they get labeled as autism they get all sorts of help at school,” he added.

Hatchwell has helped found a biotechnology company called Population Diagnostics Inc. to develop DNA based pre-symptomatic and early detection tests for autism, Alzheimer’s, Parkinson’s, Type 2 diabetes and other genetic diseases.

In 2004 researchers at Yale University found one child with developmental delays who had a deleted copy of contactin 4. In January, they and two other teams linked a gene called contactin associated protein-like 2 with some cases of autism, and a third team found a stretch of DNA on chromosome 16 that they said may cause 1 percent of autism cases.

Editing by Cynthia Osterman