A 40-year-old man develops choreiform movements and progressive cognitive decline. His father had similar symptoms beginning in his thirties. MRI shows symmetric atrophy of the caudate nuclei with boxcar ventricles. The pathogenesis involves expansion of which repeat sequence, and what is the effect on the encoded protein?

• A CGG expansion causing methylation silencing of FMR1
• B GAA expansion causing loss of frataxin expression
• C CAG expansion producing polyglutamine-expanded huntingtin with toxic gain of function ✓
• D CTG expansion producing sequestration of myotonic dystrophy protein kinase mRNA

Explanation

Huntington disease is an autosomal dominant CAG trinucleotide repeat expansion in the HTT gene on chromosome 4p, encoding huntingtin with an expanded polyglutamine tract. The mutant protein gains a toxic function, aggregates, and causes preferential neuronal loss in the caudate and putamen, giving chorea and dementia. CGG expansion causes fragile X syndrome, GAA expansion causes Friedreich ataxia, and CTG expansion causes myotonic dystrophy.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.