Feng Y, Lakkis L, Devys D, Warren S T
Howard Hughes Medical Institute, Emory University School of Medicine, Atlanta, GA 30322.
Am J Hum Genet. 1995 Jan;56(1):106-13.
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.
我们报告了对来自男性前突变携带者细胞中FMR1基因表达的研究。结果表明，具有前突变范围内CGG重复长度的FMR1基因转录正常。重复长度被忠实地转录到FMR1 mRNA中，通过核糖核酸酶保护测定，其稳态水平与正常细胞相似。前突变转录本也显示具有正常的周转，FMR1 mRNA半衰期估计为12小时。在正常和前突变细胞系中，FMR1蛋白的测量结果也显示丰度相似。这些数据支持脆性X综合征前突变携带者的非外显状态，并表明偶尔出现的相反病例报告可能反映其他原因，包括较大甲基化FMR1等位基因的低水平嵌合，或者仅仅是巧合。
