A 45-year-old man develops progressive choreiform movements, personality changes, and cognitive decline. His father had similar symptoms beginning at age 52. Genetic testing shows 48 CAG repeats in the HTT gene. Which statement about this condition is correct?
- A The patient's children are at risk for earlier onset due to anticipation, especially if the father transmits the allele ✓
- B The expanded CAG repeat is located in a noncoding region of the HTT gene
- C The mutation results in loss of function of the huntingtin protein
- D Pathologically, the caudate nucleus is relatively spared compared to the putamen
Correct answer: A. The patient's children are at risk for earlier onset due to anticipation, especially if the father transmits the allele
Explanation
Huntington disease is caused by CAG trinucleotide repeat expansion in the coding region of HTT (exon 1), producing a toxic polyglutamine tract (gain of toxic function). Anticipation occurs, particularly with paternal transmission, because the repeat is unstable during spermatogenesis and tends to expand further. The caudate nucleus shows the most prominent atrophy, not sparing. The repeat is in the coding region, not a noncoding region.
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.