USC researchers net $6.3M federal grant to study fragile X mutations
Focus is on premutations that lead to health problems in children, adults
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Researchers at the University of South Carolina (USC) have received $6.3 million in federal funding to study how fragile X premutations — genetic mutations that do not cause overt symptoms of fragile X syndrome but can still lead to health problems — affect children and adults.
The Center of Excellence grant, awarded by the U.S. National Institutes of Health (NIH), will enable the scientists to gain a deeper understanding of the unique health issues affecting people with fragile X premutations. The team also aims to find solutions for those issues that improve the lives of people with fragile X and related conditions.
“Our work will improve understanding of how fragile X-associated conditions develop and change over time, leading to better diagnosis and treatment for individuals across the lifespan,” Jane Roberts, PhD, executive director of the Carolina Autism and Neurodevelopment Research Center at USC, said in a university news story announcing the funding.
“This Center of Excellence grant brings together scientists, clinicians and community partners committed to improving the quality of life for people affected by fragile X,” Roberts said. “We are proud to be a national leader in this effort.”
Fragile X syndrome is caused by excessive repeats of three DNA building blocks — together known as CGG — in the FMR1 gene, which is located on the X chromosome. This gene contains instructions for producing a protein called FMRP, which facilitates communication between nerve cells.
USC researchers have studied fragile X for over 20 years
In people with the fragile X, CGG is repeated more than 200 times. However, some people carry FMR1 premutations, meaning they have fewer repeats — between 55 and 200 — in the FMR1 gene. While these people do not develop symptoms of fragile X syndrome, they are at risk of other fragile X-associated health problems.
FMR1 premutations are thought to affect approximately 1 in 150 women and 1 in 268 men.
The new research will build on nearly two decades of study into fragile X syndrome at USC, according to the university. Early work at USC found that infants carrying FMR1 premutations were more likely to show signs of anxiety and autism. Before this discovery, doctors had believed fragile X premutations did not affect young children.
Now, the grant will support the first long-term study ever to follow children with FMR1 premutations from infancy through their first five years of life.
“This study will allow us to better understand how, when, and why anxiety and autistic features develop in young children with the FMR1 premutation,” said Abigail Hogan, PhD, a professor at USC’s Arnold School of Public Health. “This knowledge will lead to earlier identification and diagnosis, which in turn facilitates early interventions that can help children learn and grow, and can help ensure the best possible outcomes for children and their families.”
By taking a lifespan approach — studying infants through adults — we can uncover how age, biological sex and life experiences influence the development of fragile X conditions. … The overarching goal is to identify signs and biological pathways that could lead to earlier detection and better treatment options.
Another study supported by the grant will focus on adult women, ages 35 to 80, to understand how FMR1 premutations affect the brain as people age. Women have often been excluded from research on fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative disease associated with the FMR1 premutation. This project aims to shed light on how this disease affects them.
“For years, women have been left out of the FXTAS picture, and that’s meant a lot of uncertainty for families,” said Jessica Klusek, PhD, also a professor of public health. “Our goal is to change that by giving women with the FMR1 premutation clearer information about their health risks and how those risks may evolve over time.”
Klusek added: “This will bring us closer to early and accurate diagnoses, better monitoring, and eventually better treatments for women with FXTAS.”
Together, these studies examine fragile X syndrome and associated conditions across a person’t whole life, Roberts noted.
“By taking a lifespan approach — studying infants through adults — we can uncover how age, biological sex and life experiences influence the development of fragile X conditions,” Roberts said. “The overarching goal is to identify signs and biological pathways that could lead to earlier detection and better treatment options. Ultimately, this supports thousands of patients and their families.”
