National Fragile X Center at Emory
Promoting excellence in research, clinical care and education
Center Director: Stephen T. Warren, PhD
Center Co-Director: Stephanie Sherman, PhD
The National Fragile X Center at Emory is focused on improving the lives of people with Fragile X-Associated Disorders through research, clinical care, and education. At Emory, we have been involved in this goal since the alteration (called mutation) of the FMR1 gene was first identified by Dr. Stephen Warren in the early 1990s as the leading cause of fragile X syndrome. Most recently, the National Institutes of Health has provided additional support for this Center to support its work. This makes Emory one of the three National Fragile X Centers in the U.S. These Centers are committed to working together to make rapid progress towards prevention and treatment of fragile X syndrome (FXS), fragile X-associated tremor/ataxia syndrome (FXTAS), and fragile X-associated primary ovarian insufficiency (FXPOI).
Fragile X Syndrome (FXS)
FXS is the leading genetic cause of intellectual disability and the most common single-gene cause of autism spectrum disorder (ASD). It is caused by the expansion of the trinucleotide repeat (CGG) in the 5’ untranslated region of the FMR1 gene to over 200 repeats. When the repeat is this big, it becomes methylated, a process that silences the gene. This “full” mutation leads to the lack of FMRP, the protein product of FMR1. Because the FMR1 gene is located on the X chromosome, males are typically more severely affected than females, but there is a wide range of severity.
Fragile X-associated tremor/ataxia syndrome (FXTAS)
FXTAS is a late-onset disorder that typically begins with motor symptoms of intention tremor and imbalance (ataxia) in the late 50s. Eventually motor symptoms are accompanied by cognitive problems. Males are typically more often (30-40% risk) and more severely affected than females (10-15% risk). FXTAS is due to the “pre”mutation in the FMR1 gene. The premutation is defined as having 55-200 (unmethylated) repeats. The disorder is caused by the consequence of the long repeat track in the FMR1 mRNA.
Fragile X-associated primary ovarian insufficiency (FXPOI)
FXPOI leads to ovarian dysfunction prior to age 40. It occurs in about 20% of women who carry the premutation. FXPOI can lead to sub-fertility, early menopausal-related symptoms (e.g., hot flashes, depression, anxiety) and to early onset of disorders associated with estrogen deficiency (e.g., loss of bone mineral density increasing risk for fractures, cardiovascular disease). It is caused by the premutation, most likely because of the long repeat track in the FMR1 mRNA.