The Centers for Collaborative Research in Fragile X and FMR1-Associated Conditions (“Fragile X Centers”) Program supports research to improve the diagnosis and treatment of Fragile X syndrome (FXS) and other conditions associated with mutations in the FMR1 gene. These centers are geared toward stimulating multidisciplinary, multi-institutional research, with the common goal of facilitating the translation of basic research findings from bench to bedside and bedside to community.
The first Fragile X Centers were funded in 2003, in response to the Children’s Health Act of 2000. The program currently comprises the three multi-institution centers listed in the Current Sites section. The centers are administered through NICHD’s Intellectual and Developmental Disabilities Branch, with additional support from the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke.
FXS is caused by an unstable expansion of a three base-pair (CGG) repeat on the FMR1 gene, located on the long arm of the X chromosome. When these expansions exceed a certain size, called a “full mutation,” they lead to FXS in affected males and some affected females. Shorter, but still longer-than-typical expansions, called “premutations,” are associated with risk of developing certain FMR1-associated conditions in adulthood, including Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) and Fragile X-Associated Primary Ovarian Insufficiency (FXPOI).
Since their inception, NIH Fragile X Centers have conducted research relevant to both the FMR1 full mutation and the FMR1 premutation. Specific Center research areas include genetics, proteomics, neurobiology, pathophysiology, epidemiology, and behavioral studies.
Past center studies have included:
- Examination of large-scale brain activity in mouse models and humans to determine the causes of heightened sensitivity to sound in FXS
- Evaluation of molecules that seem to play important roles in FXS to identify possible targets for future drug development
- Identification of possible additional genes associated with likelihood of developing premutation conditions (FXTAS and FXPOI) and of developing certain features of FXS (epilepsy)
- Determination of the full phenotypic spectrum of genetic changes in the FMR1 gene and identification of pathological causes of various FXS symptoms, with the aim of discovering and testing effective treatments
- Functional and structural roles of the antisense transcript of the FMR1 gene, including possible molecular and clinical correlations with Fragile X-associated tremor/ataxia syndrome, an adult-onset disease associated with FMR1 mutation
- Restoration of partial function to the Fragile X protein in conditional mouse mutants, which vary by regional and temporal levels of FMR1 expression
- Evaluation of early developmental processes that lead to the variable epigenetic inactivation of FMR1 in human cells
- Newborn screening, including methods of testing immediate and extended family members, and the impact of newborn screening on the family
- Development of maternal responsivity to children with FXS
- Identification of unique challenges faced by families with children, adolescents, and adults with FXS, with the goal of determining how public health-oriented programs can be of assistance in addressing these challenges
- Baylor College of Medicine, Houston
- Collaborating with Emory University, Atlanta, and the University of Michigan
- Cincinnati Children's Hospital Medical Center
- Collaborating with the University of California, Riverside, and the University of Texas Southwestern Medical Center
- Fragile X Center at Emory University, Atlanta
- Collaborating with New York University, Pennsylvania State University, Stanford University, and the University of Southern California