Trinucleotide Repeats: Fragile X Syndrome
What are trinucleotide repeats?
DNA (deoxyribonucleic acid) is the chemical that makes up our genes. It contains a "code" of 3-letter words known as "codons" or "trinucleotides." Many genes normally contain trinucleotide sequences that can be repetitive. These are called "trinucleotide repeats." But when the number of trinucleotide repeats increases to a larger than normal number of copies, the DNA is changed. The gene may not function as it should, or may not work at all.
Researchers don't know exactly 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 people are said to be "premutation carriers." When they pass on these extra copies to a child, however, those extra trinucleotide repeats cause the DNA to become unstable, the repeats within that gene expand 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.
What 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, anxiety, trouble paying attention, 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 5 to 44 trinucleotide repeats. Premutation carriers have about 55 to 200 trinucleotide repeats. People with fragile X syndrome full mutation have over 200 repeats.
June 16, 2018
Basic principles of genetic disease, Up To Date
Freeborn, Donna, PhD, CNM, FNP,Haldeman-Englert, Chad, MD