Quantitative comparison of FMR1 gene expression in normal and premutation alleles.

摘要

We report studies on FMR1 gene expression in cells derived from male premutation carriers. Transcription of FMR1 genes with CGG-repeat lengths within the premutation range was demonstrated to be normal. Repeat lengths are faithfully transcribed into FMR1 mRNAs, which have steady-state levels, as measured by RNase protection, similar to those of normal cells. Premutation transcripts also are shown to have normal turnover, with the FMR1 mRNA half-life estimated to be 12 h. Measurement of FMR1 protein was also found to be in similar abundance in normal and premutation cell lines. These data support the nonpenetrant status of premutation carriers of fragile X syndrome and suggest that the occasional case reports to the contrary may reflect either other causes, including low-level mosaicism for larger, methylated FMR1 alleles, or simply coincidence.