Smeets H J, Smits A P, Verheij C E, Theelen J P, Willemsen R, van de Burgt I, Hoogeveen A T, Oosterwijk J C, Oostra B A
Department of Human Genetics, University Hospital Nijmegen, The Netherlands.
Hum Mol Genet. 1995 Nov;4(11):2103-8. doi: 10.1093/hmg/4.11.2103.
The fragile X syndrome is associated with an expanding CGG repeat in the 5' untranslated region of the first exon of the FMR1 gene. Subsequent methylation of the promoter region inhibits expression of the FMR1 gene. In two clinically normal brothers large, expanded CGG repeats and cytogenetically visible fragile sites were found. The FMR1 promoter was unmethylated and both RNA and protein could be detected. This indicates that inactivation of the FMR1 gene and not repeat expansion itself results in the fragile X phenotype. We conclude that repeat expansion does not necessarily induce methylation and that methylation is no absolute requirement for the induction of fragile sites.
脆性X综合征与FMR1基因第一个外显子5'非翻译区的CGG重复序列扩增有关。启动子区域随后的甲基化会抑制FMR1基因的表达。在两名临床正常的兄弟中，发现了大的、扩增的CGG重复序列以及细胞遗传学上可见的脆性位点。FMR1启动子未甲基化，RNA和蛋白质均可检测到。这表明FMR1基因的失活而非重复序列扩增本身导致了脆性X综合征的表型。我们得出结论，重复序列扩增不一定会诱导甲基化，并且甲基化并非诱导脆性位点的绝对必要条件。
