Scientists, led by a team at Washington University School of Medicine in St. Louis, have linked mutations in a single gene to autism in people with neurofibromatosis type 1. The findings may lead to a better understanding of the genetic roots of autism in the wider population. [Michael Worful]
Scientists, led by a team at Washington University School of Medicine in St. Louis, have linked mutations in a single gene to autism in people with neurofibromatosis type 1. The findings may lead to a better understanding of the genetic roots of autism in the wider population. [Michael Worful]

A team of researchers, led by investigators at Washington University School of Medicine (WUSM), has linked mutations within a single gene—typically causing a rare tumor syndrome usually diagnosed in childhood—to autism. The scientists are optimistic that their recent findings in patients with neurofibromatosis type 1 (NF1) may lead to a better understanding of the genetic roots of autism in the wider population.

The researchers analyzed 531 patients from six clinical centers in the United States, Belgium, the United Kingdom, and Australia. They found that mutations in the NF1 gene that cause the disease also contributed to autistic behaviors in almost half of the NF1 patients.

“NF1 is caused by mutations in a single gene—NF1,” explained lead study investigator Stephanie Morris, M.D., an instructor in neurology at WUSM. “Our research indicates that this single gene also is associated with autism spectrum disorders in these same patients. That may make it possible to look downstream from the gene to find common pathways that contribute to autism in the wider population.”

The findings from this new study were published recently in JAMA Psychiatry in an article entitled “Disease Burden and Symptom Structure of Autism in Neurofibromatosis Type 1.”

NF1 is a result of mutations in the NF1 gene, which provides instructions for making the tumor suppressor protein neurofibromin. This protein is produced in a variety of cell types, including nerve cells, oligodendrocytes, and the Schwann cells that surround nerves. Symptoms can vary in severity, but often include flat, brown “café au lait” spots on the skin. Other symptoms include tiny nodules on the iris of the eye, nerve tumors, bone deformities such as a curved spine or a bowed lower leg, and optic gliomas, which are tumors of the optic nerve. Children with NF1 also can have learning disabilities. 

“In the 25-plus years that I've taken care of kids with NF1, we've only recently started to recognize that these children also often have symptoms of autism,” remarked co-senior study investigator David Gutmann, M.D., Ph.D., professor of neurology and director of the Washington University NF Center. “In the past, we didn't really understand the association between NF1 and autism, but now we have new insights into the problem, which will allow us to design better treatments for children with NF1 and autism.”

The findings from this new study could also help scientists who investigate the genetics of autism understand how mutations in a single gene can contribute to symptoms of autism, such as problems with social and language skills and repetitive behaviors.

Roughly 100,000 people in the United States have NF1, which is equally common among both sexes and in all ethnic groups. Autism, however, affects 1% to 2%  of all children in the United States and is four to five times more common in boys than in girls.

“What's unique about our findings is that it's likely mutations in the NF1 gene are driving most of the symptoms of autism in children with NF1,” noted co-senior study investigator, John Constantino, professor of psychiatry and pediatrics at WUSM and director of the William Greenleaf Eliot Division of Child & Adolescent Psychiatry. “Here, we have a single-gene disorder that affects a fairly large number of people and is causing autism in a significant number of those who are affected. This work could provide us with an opportunity to study a single gene and figure out what it is doing to cause autistic syndromes.”

Interestingly, since most autism spectrum disorders are influenced by multiple genes, studying and isolating this one gene could aid efforts to learn how other, unrelated genes may interact along that same pathway to contribute to autism in people who don't have NF1. Moreover, learning how those various genes come together to cause symptoms eventually could lead to better treatments.

“We've been able to screen children at our center, identify autism spectrum disorder, attention-deficit disorder, and problems with executive cognitive function,” Dr. Morris concluded. “And when we identify these deficits in kids, we can tell their parents, inform their schools, and enable these children to get the resources and support they need—specifically academic and social support—to improve their quality of life.”








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