FMRP expression as a potential prognostic indicator in fragile X syndrome

Absence or deficit of FMR1 protein (FMRP) resulting from methylation of ful l mutation genes is the fundamental defect in fragile X syndrome. We used F MRP immunocytochemistry and detailed phenotypic assessment to investigate t he relationship between degree of FMRP expression and the broad clinical sp ectrum of impairment in 80 individuals affected with fragile X syndrome. FM RP expression correlated with IQ in mosaic males (P=0.043), males with a pa rtially methylated full mutation (P=0.0005), and females with a full mutati on (P=0.046). In the females, FMRP expression also correlated with the numb er of fragile X physical features (P=0.0003). Even modest deficits in FMRP result in some manifestations of fragile X syndrome. In this initial study of 53 males, FMRP expression testing had a very high positive predictive va lue (100%, confidence interval of 29-100%) for a nonretarded IQ among males with expression of FMRP in greater than or equal to 50% of lymphocytes (3 males), suggesting that FMRP expression may have potential as a prognostic indicator in males with fragile X syndrome. (C) 1999 Wiley-Liss, Inc.