Validity of analysis of FMRP expression in blood smears as a screening test for Fragile X Syndrome in the Indian population

Abstract

Molecular diagnosis of Fragile X Syndrome (FXS) is carried out by PCR or Southern blot analysis on DNA isolated from leukocytes. These DNA analyses are time consuming and expensive, making it impractical for mass screening programs. We have recently standardized and tested the diagnostic potential of a rapid antibody test on blood smears, based on the presence of FMRP, the protein product of the FMR1 gene, in lymphocytes from normal individuals and the absence of FMRP in lymphocytes in patients with FXS. This test is essentially similar to the one developed at Erasmus University in the Netherlands, with suitable modifications. The diagnostic power of the antibody test is perfect for males, whereas the results are less specific for females. The cutoff value for affected male individuals, expressed as the percentage of FMRP-positive cells, was 20%. In normal individuals, the cutoff value was 85%. The results of the antibody test correlated well with that of Southern blots. Sensitivity of the test was 100% and specificity was 97.5%. This noninvasive test requires one or two drops of blood and is rapid, simple, and cheap, making it an ideal choice for large screening large groups of male mental retardates and neonates for FXS in developing countries such as India.