Immunohistochemical FMRP studies in a full mutated female fetus

Fragile X syndrome (FXS) is the most common form of inherited mental retardation. Clinical manifestations are due to the absence of the FMRP protein. Affected patients have widely variable phenotypes which are more variable in females than males, presumable due to X inactivation. We report the expression pattern of FMRP in cerebral cortex and ovary in a control and a full-mutated female fetus. FMRP was expressed in mutated and control fetal tissues, although at different levels and patterns. Control fetal cerebral cortex showed FMRP expression in almost all cells, whereas the full mutation carrier showed FMRP positivity in roughly 50% of cortical cells without any specific pattern. In the ovary samples, FMRP expression was seen in all germ cells surrounded by FMRP-negative paragranulosa and interstitial cells. The Mullerian epithelium of the fetal Fallopian tube was continuously positive in the control case, whereas the full mutation carrier showed a discontinuous patchy pattern. Expression of homologue proteins FXR1P and FXR2P showed no differences between control and full mutation fetuses. The pattern of FMRP expression in full mutation carrier females is in agreement with a random X-inactivation in maturing fetal tissues. Immunohistochemical results on cerebral tissues provide a clue for the variation of mental affection among female carriers, depending not only on the number of cells devoid of FMRP, but also on the ultimate destination of those cells in sensitive or more silent location for a proper cerebral development. (C) 2003 Wiley-Liss, Inc.