Which condition is a classic example of an autosomal dominant trinucleotide repeat disorder caused by a CAG expansion?

Which condition is a classic example of an autosomal dominant trinucleotide repeat disorder caused by a CAG expansion?

• A. Huntington disease
• B. Cystic fibrosis
• C. Hemophilia
• D. X-linked disorders

Answer: (A)

Huntington disease is the best answer because it is the classic autosomal dominant trinucleotide repeat disorder caused by a CAG expansion. The CAG repeats in the HTT gene encode a polyglutamine tract in the huntingtin protein; when repeats exceed a threshold, this toxic expansion leads to progressive neuronal degeneration, especially in the striatum and cortex. The disorder shows anticipation—the age of onset can be earlier in subsequent generations due to increasing repeats during gamete formation, often with paternal transmission. The other options don’t fit this pattern: cystic fibrosis results from autosomal recessive mutations in CFTR, not a CAG repeat; hemophilia is typically X-linked; “X-linked disorders” refers to a broad category rather than a specific trinucleotide repeat condition.

Huntington disease is the best answer because it is the classic autosomal dominant trinucleotide repeat disorder caused by a CAG expansion. The CAG repeats in the HTT gene encode a polyglutamine tract in the huntingtin protein; when repeats exceed a threshold, this toxic expansion leads to progressive neuronal degeneration, especially in the striatum and cortex. The disorder shows anticipation—the age of onset can be earlier in subsequent generations due to increasing repeats during gamete formation, often with paternal transmission. The other options don’t fit this pattern: cystic fibrosis results from autosomal recessive mutations in CFTR, not a CAG repeat; hemophilia is typically X-linked; “X-linked disorders” refers to a broad category rather than a specific trinucleotide repeat condition.