UC Davis researchers develop new test for fragile X syndrome

Photo of Dr. Paul Hagerman © 2009 UC Regents
Molecular geneticist Paul Hagerman says the new test may help explain the varying cognitive, behavioral and neuropsychological difficulties that characterize fragile X syndrome.

Researchers at UC Davis have developed a new test that will measure the protein deficit responsible for fragile X syndrome — the single-most common cause of intellectual impairment and the most-commonly inherited cause of autism.

The test, described in a study in the July 2009 issue of The Journal of Molecular Diagnostics, is the first to measure an individual’s level of the fragile X mental retardation 1 (FMR1) protein.

Fragile X syndrome is the result of low levels of the FMR1 protein, which is known to play a role in communication between nerve cells. In patients with fragile X syndrome, a sequence of one cytosine and two guanine bases (CGG) in the FMR1 gene, repeated 10 to 40 times in normal individuals, is expanded to more than 200 repeats, leading to gene silencing and decreasing levels of the protein.

Study senior author Paul J. Hagerman, a professor in the Department of Biochemistry and Molecular Medicine in the UC Davis School of Medicine and director of the NeuroTherapeutics Research Institute (NTRI), said the study describes “a powerful tool to further investigate the relationship between FMR1 and the broad range of clinical involvement in fragile X syndrome.”

Existing tests for fragile X syndrome determine the presence of the fragile X mutation by measuring the number of CGG repeats in the gene. The new test, called ELISA — for enzyme-linked immunosorbent assay — measures the level of FMR1 protein (FMRP) in individuals with the mutated gene.

About the Fragile X Research and Treatment Center

Photo of UC Davis MIND Institute © 2009 UC Regents

The UC Davis MIND Institute established the Fragile X Research and Treatment Center in 2001 to achieve two important goals:

  • Support important advances in our understanding of fragile X
  • Develop interventions that improve the quality of life for people with fragile X syndrome and related conditions, including fragile X-associated tremor ataxia syndrome (FXTAS) and premature ovarian failure (POF)

In achieving these goals, the center unites specialists in pediatrics, molecular genetics, psychiatry, psychology, neurology, genetic counseling, speech and language pathology, occupational therapy, neurobiology, pathology, functional magnetic resonance imaging and social work. For more information, visit the MIND Institute online.

Photo of Randi Hagerman © 2009 UC Regents"This test is quantitative and we think it will correlate with clinical involvement, including the cognitive and behavioral problems that are part of fragile X syndrome."
—  Randi Hagerman

“This test is quantitative and we think it will correlate with clinical involvement, including the cognitive and behavioral problems that are part of fragile X syndrome. In addition, some carriers may be mildly deficient in this protein and we will see how this deficit relates to the emotional and attention problems that some experience” says Randi Hagerman, professor of pediatrics and director of the Fragile X Treatment and Research Center at the UC Davis MIND Institute.

In addition to fragile X syndrome, deficits in FMRP are linked to a variety of disorders, including developmental delay, behavioral difficulties, anxiety and attention-deficit/hyperactivity disorder (ADHD). Altered FMRP levels may also contribute to clinical involvement in children who carry smaller numbers of ("premutation”) CGG expansions, a neurodegenerative disorder called fragile X-associated tremor/ataxia syndrome (FXTAS) and primary ovarian insufficiency.

Other study authors include Christine Iwahashi, Dag Yasui and Greg Mayeur of the Department of Biochemistry and Molecular Medicine in the UC Davis School of Medicine; Randi Hagerman and Flora Tassone of the UC Davis MIND Institute; Danh Nguyen of the UC Davis Department of Public Health Sciences; and George Parrott of the CSU Sacramento Department of Psychology.

The study was funded by grants from the National Institutes of Health Interdisciplinary Research Consortium, the National Center for Research Resources and the UC Davis MIND Institute.