The FXSRC Program supports research to improve the diagnosis and treatment of Fragile X syndrome (FXS) and its related conditions. The FXSRCs 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 Program was previously funded through the Intellectual and Developmental Disabilities Branch (IDDB). The Branch initially funded three FXSRCs in fiscal year 2003 in response to the Children’s Health Act of 2000, which provided for the establishment of at least three FXSRCs to conduct and support basic and biomedical research into the detection and treatment of FXS.
These three FXSRCs successfully recompeted in 2008 and each worked with several collaborating sites at academic institutions across the country. Each FXSRC included both basic and clinical research programs, and several projects focused on newborn screening for FXS and the familial implications of that screening, improved diagnosis of FXS, and the development of assays to test the efficacy of interventions in murine models of the condition.
The Centers were recompeted in 2014 as the Centers for Collaborative Research in Fragile X ( U54) in collaboration with the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute of Mental Health (NIMH).
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. FXSRC research areas include genetics, proteomics, neurobiology, pathophysiology, epidemiology, and behavioral studies.
Past FXSRC studies include and have included :
- Examination of brain circuits in mouse models and humans to determine the causes of heightened sensitivity to sound in FXS;
- Evaluation of molecules that seem to play important underlying roles in FXS to identify possible targets for future drug development;
- Identification of possible additional genes associated with likelihood of developing epilepsy in boys with FXS, FXTAS, and FXPOI in females ;
- 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 (FXTAS), an adult-onset disease associated with FMR1 mutation;
- Restoration of partial function to the Fragile X protein (FMRP) 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 embryonic stem cells;
- Newborn screening, including methods of testing immediate and extended family members, and the impact of newborn screening on the family;
- Development of and 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.
- University of Texas Southwestern Medical Center, Dallas
- University of Massachusetts Medical School, Worcester (in collaboration with Emory University, Atlanta, and New York University)
- Emory University