Screening with the FMR1 protein test among mentally retarded males

The fragile X syndrome is characterized by X-linked mental retardation with additional features such as a long face with large protruding ears, macroo rchidism, and eye-gaze avoidance. The disorder is caused by an abnormally e xpanded CGG repeat within the first exon of the fragile X mental retardatio n (FMR1) gene that is associated with shutdown of transcription and absence of the fragile X mental retardation protein (FMRP). Detection of patients and carriers of the fragile X syndrome is done by DNA analysis of the CGC r epeat, whereas the FMRP antibody test allows rapid detection of male patien ts using bloodsmears. In a screening program for the fragile X syndrome in the southwest of the Netherlands, 412 males with mental retardation of unkn own cause were subjected to the protein test. The patients were scored for fragile X features and their DNA tested for the FMR1 mutation, as reported previously. The FMRP test detected two fragile X patients with a repeat exp ansion in FMR1, whereas normal protein expression was observed in all the r etarded male patients with a normal repeat. The FMRP test was found to be s uitable for screening among a large population of retarded males. The resul ts also suggest that mutations other than the CGG repeat leading to absence of detectable FMRP are apparently rare among mentally retarded males.