Gene Mutated In Cancer Found In Some With Autism

The gene, known as PTEN, was found to be changed, or mutated, in three of 18 people with larger than normal heads and autism spectrum disorder. Autism spectrum disorder includes classical autism, Rett syndrome and other conditions.

The study was led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital (OSU CCC-James) and Richard J. Solove Research Institute and at Children’s Mercy Hospitals and Clinics, Kansas City, Mo.

Inherited gene mutations in the PTEN gene are seen in Cowden syndrome, a poorly recognized disorder that increases a person’s risk of developing cancers of the breast, thyroid and uterus. PTEN mutations are also found in several non-inherited (i.e., spontaneous) cancers, including thyroid and endometrial cancers and some brain tumors.

The findings, published in the April Journal of Medical Genetics, raise the possibility that some people with autism and large heads may have an increased risk of cancer.

“If our findings are verified, I think that patients with classical autism or autism spectrum disorders and who have large heads should be offered genetic counseling and testing for PTEN mutations,” says principal investigator Charis Eng, professor of internal medicine and director of the clinical cancer genetics program at the OSU CCC-James.

“Those with PTEN mutations should be offered cancer surveillance like anyone with Cowden syndrome or other syndromes involving PTEN mutations and an elevated risk of cancer.”

PTEN is a tumor-suppressor gene, and normally helps prevent cells from becoming cancerous. When a mutation silences tumor-suppressor genes, it can place a person at higher-than-usual risk of developing cancer during his or her lifetime.

Autism is a developmental disorder that typically appears by age 3. It has a prevalence of four to 10 cases per 10,000 people. It is three to four times more common in males than females. People with autism typically show impaired social interactions; impaired verbal and nonverbal communications; repeated body movements, such as hand flapping or rocking; attachment to objects; and resistance to changes in routine.

This study involved 18 children 3 to 18 years of age and diagnosed with ASD and having an enlarged head, a condition known as macrocephaly. The patients’ head circumference placed them in the 97th to 99th percentile for head size for their age and sex.

Twelve of the 18 patients were identified during clinic visits; six, who had classic autism and macrocephaly, were selected from the Autism Genetic Resource Exchange, a gene bank for autism.

Of the 18 patients, three males (17 percent) age 2 to 4 years showed mutations in the PTEN gene. The locations of the mutations in the PTEN gene are different from those seen in people with cancer, Eng notes, but that may not matter.

“Tumor suppressor genes can be silenced in many ways,” she says, “and if the gene does not function, it can raise the lifetime risk of cancer.”

The paper’s first author is Merlin G. Butler, Children’s Mercy Hospitals and Clinics. Other OSU researchers involved in this study were Xiao-Ping Zhou, research scientist, and Robert Pilarski, genetic counselor.

Funding from the Children’s Mercy Hospitals Special Gift Funds, the Children’s Mercy Hospitals Physician Scientist Award, the Hall Foundation and the American Cancer Society supported this research.