The fragile X syndrome is one of the most common inherited forms of mental retardation. Prenatal diagnosis of fetus with this syndrome is of essential clinical and counseling importance. Unfortunately, most attempts to use cytogenetic preparatíons of fetal blood lymphocytes, amniotic cells or chorionic villi as a prenatal diagnostic method were not impressively successful. The present study was thus aimed to develop an unequivocal, reproducible and less
invasive diagnosis technique which might be later applied for prenatal diagnosis of the presence of fragile X chromosomes. We demonstrated that the expression of fragile X chromosomes were inducible with treatments of fluorodeoxyuridine (FudR) or methotrexate (MTX) to fibroblasts cultured in different media containing different including agents expressed their fragile X chromosomes with great differences. The observed great difference in inducibility of fragile X might well be one of the major reasons for failure in similar studies done by others. To validate our data from cytogenetic preparations, we also used the genomic DNA probe StB12.3 from the gene fragile X related mental retardation-1 (FMR-1) to detect the methylation status of CpG island and the CGG repeats increased in FMR-1 in fibroblasts from same patients. A perfect match between data from cytogenetic and molecular detections was observed. With great confidence, we reported the development of a cytogenetic detection method and its potential application for prenatal diagnosis of fragile X syndrome.
