CAG trinucleotide repeat

The CAG trinucleotide repeat is a genetic mutation associated with Huntington disease, a rare, inherited neurological disorder. This mutation occurs in the HTT gene, leading to an abnormal protein called huntingtin. The repeated CAG segments result in long stretches of the amino acid glutamine, causing protein clumps that damage nerve cells in the brain, particularly in the basal ganglia, which control movement.1

Symptoms, typically appearing between ages 35 and 50, include involuntary movements and cognitive decline. The severity and progression of Huntington disease are linked to the length of the CAG repeat, and the repeat can expand across generations, leading to earlier onset of symptoms (anticipation). Diagnosis is confirmed through genetic testing that counts the CAG repeats. Currently, there is no cure, but treatments focus on managing symptoms, with promising gene-editing and gene therapy approaches in clinical trials.12