Researchers awarded $2.4M NIH grant to study leading genetic cause of autism

University of Kansas researchers have been awarded a five-year, $2.4 million grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development to study the effects of parenting on the development and behavior of adolescents with Fragile X syndrome, a single-gene disorder that is the most common cause of inherited developmental disability and the leading genetic cause of autism.

The award will allow University Distinguished Professor Steven Warren and Associate Professor Nancy Brady, both with the Department of Speech-Language-Hearing: Science & Disorders, to continue a 10-year longitudinal study of the effect of parenting on 55 children with FXS, now adolescents, and their mothers.

“Because this is one of the longest studies ever on individuals with FXS, we can ask fundamental questions about the relationships between environment and development over time that other people can’t,” Warren said.

Among those questions is how parenting behaviors, measured across early and middle childhood, influence the adolescents’ developmental trajectories and how these trajectories vary based on child gender, autism status and molecular measures of genetics.

“We will be partnering with Elizabeth Berry-Kravis, professor of pediatrics, neurological sciences and biochemistry at the Rush University Medical Center in Chicago, to learn how biological markers in both children and mothers interact with environmental variables to affect development,” Brady said.

The study includes mothers not only because are they a potent influence on their children’s intellectual and social development but also because female carriers of the mutation in the FMR1 (Fragile X) gene often start showing some symptoms of the disorder such as anxiety and depression in their 40s and 50s — about the time their children become adolescents.

A segment in the FMR1 gene on the X chromosome called the CGG triplet repeat is lengthened from the normal 5 to 40 repeats to more than 200 repeats in people with full mutation FXS. This inactivates the FMR1 gene and prevents the production of a protein crucial to neural development. But even those with fewer repeats — both males and female carriers — are at risk for certain disorders later in life. Among many other variables, the study will look for effects correlated to each mother’s number of repeats, also known as the size of an individual’s FXS premutation.

The study will also examine the extent to which the parenting that the researchers observed in early and middle childhood predicts differences in adolescent behavior and development.

‘In the first study, we were interested in a specific type of parenting-child interaction,” Warren said. “For example, when a child says ‘ball’ and the parent immediately says, ‘It’s a green ball!’ they are incidentally teaching the child that the ball has a color and that it is green. We saw powerful effects on behaviors in early vocabulary acquisition for which we found evidence even years later.” Warren said they also saw important impacts of parenting on cognition and adaptive behaviors.

Having the scientific knowledge of the dynamic interplay of children with FXS and their parents’ behavior before and after adolescence may have important implications for both science and clinical treatment, he said.

“There is a lot of research on the biology of FXS going on throughout the world, but much less on the environment’s effect over time,” Warren said. “From the environment, which variables do you choose to study? Parents are usually a daily constant in their child’s lives, and their interactions have both short-term and cumulative effects on their children’s development and behavior, good and bad. Consequently, they represent a nearly ideal environmental measure.”

Leann Smith, assistant clinical professor and senior scientist at the University of Wisconsin Waisman Center in Madison and Kandace Fleming, associate scientist at the University of Kansas Life Span Institute, are collaborators on the project.