Huntington disease is caused by expansion of which trinucleotide repeat?

• A. CAG
• B. CGG
• C. GAA
• D. CTG

Answer: (A)

Expansion of a CAG trinucleotide repeat in the HTT gene causes Huntington disease. CAG encodes the amino acid glutamine, so a longer CAG repeat creates an elongated polyglutamine tract in the huntingtin protein. This polyglutamine expansion leads to toxic gain-of-function and neuronal degeneration, particularly in the striatum, with earlier onset and greater severity as the repeat length increases (anticipation).

The other repeats are associated with different disorders: CGG expansions cause Fragile X syndrome, GAA expansions cause Friedreich ataxia, and CTG expansions cause myotonic dystrophy type 1. Therefore, the repeat expansion responsible for Huntington disease is CAG.