Research on fragile X syndrome is taking place on two fronts. Behavioral scientists are studying development, cognition, language, and aspects of individuals with fragile X syndrome that can be measured by observing behavior. Simultaneously, biological scientists, such as Dr. Annette Taylor, director at Kimball Genetics Laboratory in Denver, Colorado are studying the genetic, cellular, biochemical, and neuroanatomical aspects of fragile X syndrome. Scientists in both fields are working together to try to understand the relationship between biological and behavioral findings.

Our growing understanding of genes and their functions has led to the discovery of the protein produced by the FMR-1 gene called FMR-P. Although scientists have not yet determined the exact function of the protein, it is possible to measure the level of FMRP an individual is expressing. In 1996, behavioral scientists began working to see whether levels of protein are related to levels and rate of development.

The CFXP has one of the largest existing databases on the longitudinal development of young males with fragile X syndrome. This large behavioral data set presented an excellent opportunity to investigate whether protein expression could be a factor in explaining the variability in developmental outcome among the boys in our study. So, in 1998 additional funding was obtained from the US Department of Education for a collaborative study with Dr. Taylor and Dr. Randi Hagerman of University of Colorado to determine the genetic status of as many of our participants as possible.

Research Goals

• Provide comprehensive genetic testing of the children and mothers of children enrolled in the project to identify the size of the trinucleotide repeat sequence, methylation status, mosaic status, activation ratio, and amount of FMR1 protein that is being produced;
  
• Examine the relationship between FMR1 protein expression and developmental outcome; and
  
• Provide genetic testing for children who are known to be at risk for fragile X syndrome, specifically siblings and first cousins of children who are enrolled in the Carolina Fragile X Project.
  

Methods

Participants


• All children participating in any of the CFXP longitudinal studies (boys and girls) and their mothers were eligible for the genetic status study.
  To date 73 children (male and female) and 50 mothers have been tested in the genotype study.
  
  

Data Collection and Staff


• The procedure involves a single blood draw from each subject's arm to obtain a 1-2 teaspoon sample. Blood is drawn by the participant's regular physician or by a pediatric nurse provided by the project who travels to the participant's home. Genetic counseling is available to the individuals and families of subjects who are newly diagnosed with fragile X syndrome (i.e. siblings or cousins).
  
  

Measures


• DNA testing using the Southern Blot analysis to confirm the status of the FX gene.
  
• Immunocytochemistry of peripheral blood smears is used to determine the percentage of lymphocytes, or blood cells, expressing FMR protein.
  

Results

• Participation in this study is ongoing. However, preliminary analyses suggest that variation in FMRP does account for a small, but significant amount of variance in the level and rate of development. FMRP does not correlate with our measures of autism status.
• Bailey, D. B., Hatton, D. D., Skinner, M., & Meisbov, G. (2001). Autistic behavior, FMR1 protein, and developmental trajectories in young males with fragile X syndrome. Journal of Autism and Development Disorders, 31(2), 165-174.
• Bailey, D. B., Hatton, D. D., Tassone, F., Skinner, M., & Taylor, A. K. (2001). Variability in FMRP and early development in fragile X syndrome. American Journal on Mental Retardation, 106, 16-27.
• Hatton, D. D., Wheeler, A.C., Skinner, M.L., Bailey, D.B., Sullivan, K.M., Roberts, J.E., Mirrett, P., & Clark, R.D. (2003) Adaptive behavior in children with fragile X syndrome. American Journal of Mental Retardation.