X inactivation of the FMR1 fragile X mental retardation gene.
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.
Kirchgessner
C U
CU
Department of Genetics, Stanford University School of Medicine, CA 94305, USA.
Warren
S T
ST
Willard
H F
HF
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004303:Dosage Compensation, Genetic; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics*; D006801:Humans; D006822:Hybrid Cells; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D016601:RNA-Binding Proteins; D014960:X Chromosome / Q000235:genetics
D017931:DNA Primers; D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human; C497684:Fmr1 protein, mouse