THE FULL MUTATION IN THE FMR-1 GENE OF MALE FRAGILE-X PATIENTS IS ABSENT IN THEIR SPERM

Fragile X syndrome is characterized at the molecular level by amplific ation of a (CGG)n repeat and hypermethylation of a CpG island preceedi ng the open reading frame of the fragile X gene (FMR-1) located in Xq2 7.3. Anticipation in this syndrome is associated with progressive ampl ification of the (CGG)n repeat from a premutation to a full mutation t hrough consecutive generations. Remarkably, expansion of the premutati on to the full mutation is strictly maternal. To clarify this parental influence we studied FMR-1 in sperm of four male fragile X patients. This showed that only the premutation was present in their sperm, alth ough they had a full mutation in peripheral lymphocytes. This might su ggest that expansion of the premutation to the full mutation in FMR-1 does not occur in meiosis but in a postzygotic stage.