Overview

The Centers for Disease Control and Prevention estimates that one child in 110 has some version of a so-called autism-spectrum disorder. But a recent study in South Korea bumps that to an alarming one in 38, suggesting that many milder cases are going undiagnosed.

Why are so many children being diagnosed with autism these days? It’s a mystery.

Autism-spectrum disorders such as Asperger's syndrome, autism and Rett syndrome share certain characteristics, including social withdrawal. Patients also show impaired language skills, repetitive behaviors and motor disabilities. In severe cases these symptoms can affect the very tools humans have to connect with one another, to communicate, to feel empathy, to build families and friendships.

Research at The Jackson Laboratory focuses on a specific ASD, Rett syndrome, that has a genetic basis. Zhong-wei Zhang, Ph.D, is investigating the mutation that causes Rett syndrome and the role of the normal protein, MeCP2, in brain development. Insights gained have the potential to uncover the causes of Rett syndrome and other ASDs and lead to the development of improved treatment options.

Research

Assistant Professor Zhong-wei Zhang, Ph.D., is working to understand the causes of Rett syndrome as well as autism-spectrum disorders in general. "These are all developmental disorders of the brain, and they all show defective communications between neurons," Zhang says.

Autism-spectrum disorders are among the most genetic of neuropsychiatric diseases and may involve many genes important for brain development.

In the case of Rett syndrome, about 99 percent of patients have mutations on a single gene, MECP2. This gene provides instructions for making a protein that regulates the production of many other proteins in the brain. The mutations in the gene, which appears on the X chromosome, have severe developmental consequences. Because girls have two X chromosomes, a second, healthy copy of MECP2 more or less compensates for the defect. Male embryos with the mutation, lacking this second copy, seldom survive more than a few days past birth.

Zhang says he expects more Rett-related mutations to be discovered as researchers comb through the genomes of patients. "Where I think I can make a contribution," he says, "is to understand how those mutations relate to the disease and then try to come up with ideas for treatment. Ideally, we would want to design interventions that are early enough—before the onset of Rett syndrome—to prevent the disease from happening at all."

Personal Connections

Meghann Harris wants to change the future for those with Rett syndrome. Her daughter, Eliza, lives with the disorder.

Eliza was diagnosed with Rett syndrome after her first birthday. Rett syndrome is an autism spectrum disorder that shares characteristics with other disorders such as Asperger's syndrome and autism. Those characteristics include motor disabilities, impaired language skills, social withdrawal and repetitive behaviors.

In addition to Rett syndrome research here, efforts are under way to develop a mouse model based on Eliza’s rare mutation, which causes a milder form of the disorder. To date, no other Rett cases in the world have been documented to have Eliza’s specific mutation.

"The mouse models that have been developed so far are the most classic mutations that are most often found in patients," said The Jackson Laboratory’s Cathy Lutz, Ph.D., who is responsible for ensuring that the best mouse models of human diseases are available to the worldwide scientific community. “But rare mutations like Eliza's could provide a window into cases of Rett syndrome that are so mild they might even escape diagnosis."

Meghann calls her little daughter "amazing" and says "she's constantly surprising people. She teaches me how to enjoy life, laugh, push through challenges and reach my goals, because that's what she does every single day. I truly believe that The Jackson Laboratory is going to find a cure for Eliza in my lifetime."