Fragile X syndrome is caused by a change (mutation) in a gene on the X chromosome’s long arm (Xq27.3). The gene is called fragile X mental retardation 1 (FMR-1). The syndrome is the most common hereditary cause of mental retardation and is passed on through X-linked recessive inheritance. Diagnosis is made through DNA-analysis of blood samples. The gene change causes a trinucleotide sequence, three genetic nucleotide bases, CGG, to be repeated too many times. Generally, this sequence is repeated in the gene between 5 and 44 times. If a person has an FMR1-gene with 55-200 CGG-triplets, a so-called premutation is present.
In cases of a full mutation, i.e. when the number of repeats of the nucleotide sequence surpasses 200, the gene is turned off. Normally the gene encodes a protein that is important for the neurons’ connection points (synapses). When the gene is turned off, that specific protein cannot be formed.
In cases of a premutation there is some production of the protein and the ones who have a premutation therefore do not get equally pronounced symptoms compared to someone with a full mutation. Men and women with a premutation are considered genetic carriers of Fragile X syndrome. However, a premutation is unstable, and may increase in size when it is transferred from mother to child. Hence, children of women with a premutation may get Fragile X syndrome. Children with a full mutation of the gene in question may have inherited the mutation from the mother, who may be a carrier of a premutation or have a full mutation themselves. Boys who have inherited a full mutation get Fragile X syndrome, but girls with a full mutation do not always get the syndrome, since they have two X chromosomes, i.e. the other X chromosome has a normally functioning gene. Daughters of fathers with premutation become premutation carriers, whose children in turn risk getting the syndrome, while a premutation cannot be inherited from father to son.