Trinucleotide Repeats: Fragile X Syndrome

DNA, the chemical that makes up our genes, contains a "code" of three-letter words known as "codons" or "trinucleotide repeats." Many genes normally contain a trinucleotide repeat which is present in several copies. But when the number of trinucleotide repeats increases to a larger than normal number of copies, the DNA is altered; therefore, the gene may not function properly, or may not work at all.

It is not well understood what causes a trinucleotide repeat to expand into more than the usual number of copies that should be in a gene. Sometimes, a person may have more than the usual number of copies, but not 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, however, those extra trinucleotide repeats cause the DNA to become unstable, and the area of DNA expands even more. The result is that the child has a gene that is not functioning properly (if at all), and the child is said to have the "full mutation." An example of a trinucleotide repeat disorder is Fragile X syndrome.

Fragile X syndrome causes intellectual disability. This can range from mild to moderate to severe, in both males and females. However, males are typically more severely affected than females. Symptoms of Fragile X syndrome in childhood are not always specific. They overlap with other disorders, such as autism, Prader-Willi syndrome, and attention deficit-hyperactivity disorder (ADHD). Symptoms may include delays in development of speech, language, and motor skills. Autistic-like behavior, frequent tantrums, and hyperactivity are also commonly seen with Fragile X syndrome. Gaze aversion, or the inability to make and hold eye contact, is very common among males and females with Fragile X syndrome.

The gene that causes Fragile X syndrome, called FMR1, is located on the X chromosome. Females are usually not as severely affected as males. That is because females have a normal X chromosome, in addition to the X with the mutation. The FMR1 gene normally contains fewer than 44 trinucleotide repeats. Premutation carriers have about 55 to 200 trinucleotide repeats. People with Fragile X syndrome full mutation have more than 200 repeats.