Expansion of CAG repeats in the HTT gene is associated with which neurodegenerative disease?

• A. Alzheimer's disease
• B. Huntington disease
• C. Parkinson disease
• D. ALS

Answer: (B)

Expansion of CAG repeats in the HTT gene causes Huntington disease because the CAG sequence encodes the amino acid glutamine, and when repeats are abnormally long, the resulting huntingtin protein contains an expanded polyglutamine tract that misfolds and aggregates. This toxic protein leads to degeneration of neurons, especially in the caudate and putamen, producing the characteristic movement disorders (chorea), along with cognitive decline and psychiatric symptoms. The HTT gene is located on chromosome 4, and disease typically shows anticipation—the earlier onset with successive generations due to further repeat expansion during meiosis. Normal alleles have a limited number of repeats, while pathogenic expansions beyond a threshold (often over about 36 repeats) cause disease. This pattern is distinct from Alzheimer's, Parkinson disease, or ALS, which have different genetic and pathogenic mechanisms.