A 45-year-old man presents with progressive choreiform movements, personality change, and cognitive decline over 5 years. His father had similar symptoms. MRI shows bilateral atrophy of the caudate nucleus and putamen with ex vacuo dilatation of the frontal horns. What is the genetic basis of this disease?

• A CAG trinucleotide repeat expansion on chromosome 6
• B CAG trinucleotide repeat expansion on chromosome 4 ✓
• C Hexanucleotide repeat expansion in C9orf72
• D Mutation in the ATP7B gene

Explanation

This describes Huntington's disease, an autosomal dominant neurodegenerative disorder caused by CAG trinucleotide repeat expansion in the huntingtin (HTT) gene on chromosome 4. The expanded polyglutamine tract causes toxic gain of function. Caudate atrophy with frontal horn dilatation is the classic imaging finding. Chromosome 6 CAG expansion is seen in spinocerebellar ataxia type 1. C9orf72 expansion causes ALS/FTD. ATP7A mutation causes Wilson's disease.

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.