Eichler E E, Richards S, Gibbs R A, Nelson D L
Institute for Molecular Genetics, Baylor College of Medicine, Houston, TX 77030.
Hum Mol Genet. 1993 Aug;2(8):1147-53. doi: 10.1093/hmg/2.8.1147.
The fragile X syndrome is due to a CGG triplet expansion in the first exon of FMR1, resulting in hypermethylation and extinction of gene expression. To further our understanding of the gene's involvement in the syndrome, we report the physical structure of this locus. A high resolution restriction map of the FRAX(A) locus has been prepared encompassing approximately 50 kb. Using exon-exon PCR and restriction analysis, the FMR1 gene has been determined to consist of 17 exons spanning 38 kb of Xq27.3. Each intron-exon boundary has been sequenced. In general, the splice donors and acceptors located in the 5' portion of the gene demonstrate greater adherence to consensus than those in the 3' end, providing a possible explanation for the finding of alternative splicing in FMR1. The elucidation of the exon composition of the FMR1 gene and its flanking region will enhance detection of coding sequence mutations possible in fragile X phenocopy individuals.
脆性X综合征是由于FMR1基因第一外显子中的CGG三联体扩增，导致基因表达的超甲基化和沉默。为了进一步了解该基因在综合征中的作用，我们报告了该基因座的物理结构。已制备了包含约50 kb的FRAX(A)基因座的高分辨率限制酶图谱。使用外显子-外显子PCR和限制酶分析，已确定FMR1基因由跨越Xq27.3 38 kb的17个外显子组成。每个内含子-外显子边界均已测序。一般来说，位于基因5'部分的剪接供体和受体比3'端的更符合共有序列，这为FMR1中发现的可变剪接提供了一种可能的解释。FMR1基因及其侧翼区域外显子组成的阐明将增强对脆性X表型模拟个体中可能存在的编码序列突变的检测。
