Trinucleotide repeat

Trinucleotide repeat disorders are a set of genetic disorders caused by trinucleotide repeat expansion, a kind of mutation where trinucleotide repeats in certain genes exceed the normal, stable threshold, which differs per gene. This type of mutation can lead to the disease in two different ways: either through a gain of function, where the repeats produce a toxic protein, or through a loss of function, where the repeats turn off the production of a necessary protein.

Types of Trinucleotide Repeat Disorders

There are several types of trinucleotide repeat disorders, each caused by repeats of a different trinucleotide. Some of the most common types include:

• Huntington's disease: This is caused by a CAG repeat in the HTT gene. The disease is characterized by progressive motor dysfunction, cognitive decline, and psychiatric disturbances.

• Fragile X syndrome: This is caused by a CGG repeat in the FMR1 gene. The syndrome is characterized by intellectual disability, hyperactivity, and physical features such as a long face and large ears.

• Myotonic dystrophy: This is caused by a CTG repeat in the DMPK gene. The disease is characterized by muscle weakness and myotonia, as well as cataracts, heart conduction defects, and endocrine changes.

• Friedreich's ataxia: This is caused by a GAA repeat in the FXN gene. The disease is characterized by progressive gait and limb ataxia, dysarthria, areflexia, and loss of vibration and position senses.

Mechanism

The mechanism of trinucleotide repeat expansion is not fully understood. However, it is believed to occur during DNA replication, repair, or recombination, when the DNA polymerase slips on the template strand and misaligns the repeat units. This results in the addition of extra repeats and the expansion of the trinucleotide repeat sequence.

Diagnosis and Treatment

Diagnosis of trinucleotide repeat disorders is usually based on clinical symptoms and confirmed by genetic testing. Treatment is mostly symptomatic and supportive, as there is currently no cure for these disorders. However, research is ongoing to find ways to prevent or reverse the repeat expansion.

See Also

• Genetic disorder
• DNA replication
• DNA repair
• DNA recombination

Trinucleotide repeat Resources
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