Affected individuals have >200 CGG repeats and are classified as having a full mutation (FM) which is associated with hypermethylation of an upstream gene promoter region (CpG island) and silencing of
FMR-1 gene transcription which results in the absence of the gene product, fragile X mental retardation protein (FMRP).
Absence of expression of the
FMR-1 gene in fragile X syndrome.
Normal variation in size of the
FMR-1 gene is not associated with variation in intellectual performance.
The severity of fragile X syndrome in an affected individual is usually related to the size of the DNA mutation within the
FMR-1 gene. Some intellectually normal people have a fragile X "premutation," or small mutation.
In these, the affected
fmr-1 gene had 57, 168, 182, 207, 266, or 285 repeats.