After Down's syndrome, fragile X syndrome is the second most frequent genetic cause of mental retardation. The disorder is one of a group of diseases that results from an unusual kind of mutation: an expansion of a repeating sequence of three letters of the DNA code, called a triplet repeat or trinucleotide repeat.

 

In fragile X, the repeating triplet is CGG, cytosine-guanine-guanine, in a gene called FMR1 on the X chromosome. There are ordinarily fewer than 55 copies of the repeat. When the number of repeats exceeds 200, the expansion is called a "full mutation" and expression of the FMR1 gene is shut off, causing the fragile X syndrome.

 

Individuals who carry between 55 and 200 copies of the repeat, called a "premutation", may transmit a gene with a full mutation (more than 200 repeats) to their children, but are generally not affected by the full-blown fragile X syndrome themselves.

 

Carriers of premutations may have difficulties with mild cognitive or behavioral problems, premature ovarian failure in female carriers,and an adult-onset neurological disorder causing tremor and difficulties with balance and gait.