Genetic scientists at Emory University School of Medicine already maintain the world's most extensive research program on fragile X syndrome, the leading cause of inherited mental retardation. Up until now, however, they have had only a rough estimate of the incidence of fragile X in the population. Using a new grant from the Centers for Disease Control and Prevention (CDC) and dried blood samples leftover from the Georgia Newborn Screening Program, the Emory scientists will try to determine the birth prevalence of fragile X in Georgia and therefore calculate the true incidence in the country.
The Georgia Newborn Screening Program already routinely screens all newborns -- approximately 134,000 each year -- for 12 genetic diseases, using a small amount of blood obtained through a heel-stick. The Emory Department of Human Genetics serves as the follow-up lab for all positive results from these tests. The blood samples are placed within small circles on an index card, but only part of the blood is needed for the current screening tests. The Emory scientists will use a fraction of the remaining dried blood spots to test for fragile X. All identifying information will be eliminated from the samples except the gender, race and ethnicity of the tested newborns. The goal of the project is to screen samples from approximately 70,000 consecutive newborns.
The researchers will use a novel technology, developed at Emory, that no one else in the world is using. This technology can detect changes in FMR1 DNA methylation, a modification of the FMR1 gene that is found in the vast majority of cases of fragile X syndrome. DNA methylation is involved in silencing of expression of the FMR1 gene resulting in the absence of the FMR1 gene product, FMRP, leading to fragile X syndrome.
"If we can determine that this testing method is feasible on such a large number of subjects, we eventually hope the test can become part of routine newborn screening, " says Emory geneticist Bradford Coffee, PhD, coordinator of the fragile X study. "Identification of these children as infants, instead of at 3 or 4 years of age as is currently done, will allow early intervention therapies to be initiated to maximize the potential of these kids. We could counsel more families about the consequences of fragile X and help them obtain support and eventually treatment, as soon as therapies are developed."
In 1991, Stephen T. Warren, PhD, chair of Emory's Department of Human Genetics and principal investigator of this new study, led an international research team that discovered the FMR1 gene, which is responsible for fragile X syndrome when the gene is abnormally silenced, or deactivated. When FMR1 is silenced, it fails to produce the FMRP protein, which leads to abnormalities in the expression of other genes required for the interaction of neurons. Depending on how these mutations manifest themselves in different cases, individuals suffer anywhere from mild to severe consequences. Even carriers of the fragile X gene may suffer negative effects, including premature ovarian failure and ataxia.
In the past few years Dr. Warren and his colleagues have identified possible drug targets that may be beneficial for fragile X syndrome. Currently they have identified four lead drugs and are investigating their efficacy in a mouse model of fragile X syndrome. If these efforts are successful, identification of newborns with fragile X, as will be done in this new study, will become critical for intervention.