The mutation, referred to as “trinucleotide repeat (TNR) expansion,” occurs when the number of triplets present in a mutated gene is greater than the number found in a normal gene [1–3]. Additionally, the number of triplets in the disease gene continues to increase as the disease gene is inherited (Fig. 1a).

What causes trinucleotide repeat expansion?

Triplet expansion is caused by slippage during DNA replication or during DNA repair synthesis. Because the tandem repeats have identical sequence to one another, base pairing between two DNA strands can take place at multiple points along the sequence.

How does repeat expansion occur?

GAA repeats expand when their repeat length is greater than the Okazaki fragment's length. These repeats are involved in the stalling of the replication fork as these repeats form a triplex when the 5' flap of TTC repeats fold back.