Fine structure of the human FMR1 gene

The fragile X syndrome is due to a CGG triplet expansion inthe first exon of FMR1, resulting in hypermethylation and extinctionof gene expression. To further our understanding of the gene'sinvolvement in the syndrome, we report the physical structureof this locus. A high resolution restriction map of the FRAX(A)locus has been prepared encompassing approximately 50 kb. Usingexon-exon PCR and restriction analysis, the FMR1 gene has beendetermined to consist of 17 exons spanning 38 kb of Xq27.3.Each intron-exon boundary has been sequenced. In general, thesplice donors and acceptors located in the 5' portion of thegene demonstrate greater adherence to consensus than those inthe 3' end, providing a possible explanation for the findingof alternative splicing in FMR1. The elucidation of the exoncomposition of the FMR1 gene and Its flanking region will enhancedetection of coding sequence mutations possible in fragile Xphenocopy individuals.