Trinucleotide Repeats:

Fragile-X Syndrome

What are trinucleotide repeats?

DNA, the chemical that makes up our genes, contains a code of three letter words, called codons or trinucleotide repeats.

Many genes normally contain a trinucleotide repeat, which is present several times. When the number of trinucleotide repeats too often, the DNA is altered and may function improperly or not at all.

It is not well understood what causes a trinucleotide repeat to grow into more than the usual number of copies for a gene. Sometimes, a person may have more than the usual number of copies without having enough to alter the function of the gene.

These individuals are referred to as premutation carriers. When they pass on these extra copies to a child, the extra trinucleotide repeats cause the DNA to become unstable. Then, the area of DNA expands even more.

The result is that the child has a gene that functions improperly or no longer functions at all. They are said to have the full mutation. An example of a trinucleotide repeat disease is Fragile-X syndrome.

What is Fragile-X syndrome?

Fragile-X syndrome causes moderate mental retardation among males and mild mental retardation among females. Symptoms of Fragile-X in childhood are not specific because the symptoms overlap with other disorders, such as autism, Prader-Willi syndrome and attention deficit-hyperactivity disorder.

Symptoms include delays to the development of speech, language and motor skills. Autistic-like behavior and hyperactivity are also common with Fragile-X syndrome. Gaze aversion, inability to make and hold eye contact, is extremely common among males and females with Fragile-X syndrome.

The gene for Fragile-X, called FMR-1, is located on the X chromosome.

Females are usually not as severely affected as males because females have a normal X chromosome along with the X chromosome with the mutation. The FMR-1 gene normally contains less than 44 trinucleotide repeats.

Premutation carriers have about 59 to 200 trinucleotide repeats, and persons with Fragile-X syndrome have more than 200 repeats.