Introduction: Fragile X syndrome (FXS) is the commonest cause of hereditary mental retardation. Although most affected patients, especially males, have a typical phenotype, molecular studies of the FMR1 gene are necessary to confirm the diagnosis, depending on the number of repeats of the CGG triplet of the gene.
Development: In recent years an immunohistochemical technique has been developed which permits the study of the expression of the protein codified by the FMR1 gene, known as FMRP (Fragile X Mental Retardation Protein). This was done initially in peripheral blood lymphocytes and more recently in hair roots, thus permitting definite identification of males affected by FXS. The advantages of this technique compared with conventional molecular studies are speed (results available in a few hours), lower cost and ease of sample obtention, that in the case of hair roots is non-invasive. The affected males had significant lower levels of FMRP expression than normal or non fragile X males, without overlapping. This finding was observed in blood and hair roots. In females, interpretation is more difficult due to random inactivation of one of the X chromosomes. However, preliminary studies have shown that the level of FMRP expression in hair roots of females with the full mutation (usually with some degree of mental retardation) is significantly lower when compared to premutation carriers or normal females.
Conclusion: The FMRP test, either in blood or hair, is an easy, cost-effective method for screening FXS in males with idiopathic mental retardation.