Many human genetic diseases stem from an unusual problem in DNA—specifically the presence of too many copies of a short DNA sequence in one important gene. The Fragile X–related disorders result from too many repeats of the sequence CGG in a gene called FMR1. Fragile X–associated tremor and ataxia syndrome (FXTAS) and Fragile X–associated primary ovarian insufficiency (FXPOI) are seen when the FMR1 gene has 55–200 repeats. FXTAS is a disorder affecting balance and walking. Memory loss, cognitive decline, and other problems are also seen frequently. FXPOI is associated with infertility and an early menopause. Females with 55–200 repeats are also at risk of having a child with Fragile X syndrome. These children have more than 200 repeats in their FMR1 gene. This results in a learning disability that is in fact the most common inherited form of intellectual disability. Affected children also often have autistic symptoms, depression, and behavioral problems.
We are interested in these diseases because they provide a window into critical processes affecting brain and ovarian function, and they affect these organs in ways that scientists do not fully understand yet. We use a number of approaches to look at how these diseases arise and their consequences.