The FMR1 gene appears in four forms that are defined by the number of repeats of a pattern of DNA called CGG repeats. DNA is made of molecules that are abbreviated A, C, G and T. A CGG repeat in the FMR1 gene is a pattern of DNA that may repeats itself anywhere from 30 to 1,000 times. In the FMR1 gene there is an area of the promoter that is rich in these CGG repeats and is measured when Fragile X testing is performed.
- Normal: Individuals with less than 45 CGG repeats have a normal FMR1 gene.
- Intermediate: Those with 45-54 CGG repeats have what is called an “intermediate” or “gray zone allele,” which does not cause any of the known Fragile X associated disorders.
- Premutation: Individuals with 55-200 CGG repeats have a premutation, which means they carry an unstable mutation of the gene that can expand in future generations and thus cause Fragile X syndrome in their children or grandchildren. Individuals with a premutation can also develop FXTAS or FXPOI themselves.
- Full Mutation: Individuals with over 200 CGG repeats have a full mutation of the FMR1 gene, which causes Fragile X syndrome.
The full mutation causes the FMR1 gene to shut down or “methylate” in one region. Methylation happens to other genes too, when they are supposed to be turned off (as in the genes we don’t use, like those that make a tail grow!).
Normally, the FMR1 gene produces an important protein called FMRP. When the gene is turned off, the individual does not make this protein. In Fragile X the methylation turns off the FMR1 gene, so no FMRP is produced.
The lack of this specific protein is what causes Fragile X syndrome.