Fragile X syndrome Is the most frequent form of inherited mental retardation and Is associated with a fragile site at Xg27.3. We identified human YAC clones that span fragile X site-induced translocation breakpoints coincident with the fragile X site. A gene (FMR-1) was identified within 8 four cosmid contig of YAC DNA that expresses a 4.8 kb message in human brain. Within a 7.4 kb EcoFII genomic fragment, containing FMR-1 exonic sequences distal to a CpG island previously shown to be hypermethylated in fragile X patients, is a fragile X site-induced breakpoint cluster region that exhibits length variation in fragile X chromosomes. This fragment contains a lengthy CGG repeat that is 250 by distal of the CpG island and maps within a FMR-1 axon. Localization of the brain-expressed FMR-1 gene to this EcoRl fragment suggests the involvement of this gene in the phenotypic expression of the fragile X syndrome.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)