The Fragile X gene

Unlike most other inherited disorders, Fragile X syndrome is not the result of a single change in the genetic code — instead there is the multiplication of part of the genetic information. Fragile X is an example of a triplet repeat disorder and one of the first to be recognized.

In 1991, scientists discovered the FMR1 gene. At the start of this gene lies a region of DNA that varies in length from one person to another. It has a sequence in which the cytosine, guanine and guanine (CGG) codon are repeated.

No Fragile X: this stretch of DNA falls within a range of length that would be considered “normal” – between 6 and 55 repeats of the CGG codon.

Premutation: this stretch of DNA is somewhat longer — from 55 to 200 CGG repeats. Although a person who carries the premutation does not typically have symptoms of Fragile X, the stretch of DNA is prone to further expansion when it is passed from a woman to her children.

Full Mutation: this stretch of DNA has expanded beyond a certain length (beyond 200 CGG repeats). The gene is switched off and does not produce the Fragile X-mental retardation protein, FMRP. A male who inherits a full mutation exhibits Fragile X syndrome because his only X chromosome contains the mutated gene. A female may not be as severely affected because each cell of her body needs to use only one of its two X chromosomes and randomly inactivates the other.