X inactivation of the FMR1 fragile X mental retardation gene

Abstract

X chromosome inactivation has been hypothesised to play a role in the aetiology and clinical expression of the fragile X syndrome. The identification of the FMR1 gene involved in fragile X syndrome allows testing of the assumption that the fragile X locus is normally subject to X inactivation. We studied the expression of the FMR1 gene from inactive X chromosomes by reverse transcription of RNA followed by PCR (RT-PCR), both in somatic cell hybrids which retain an active or inactive human X chromosome and in a female patient with a large deletion surrounding the FMR1 gene. In both analyses, the data indicate that FMR1 is not normally expressed from the inactive X chromosome and is, therefore, subject to X chromosome inactivation. This finding is consistent with the results of previous studies of DNA methylation of FMR1 on active and inactive X chromosomes, verifies previous assumptions about the fragile X locus, and supports the involvement of X inactivation in the variable phenotype of females with full mutations of the FMR1 gene.