A 38-year-old man with choreiform movements, psychiatric disturbance, and caudate nucleus atrophy on MRI is diagnosed with Huntington disease. His father was similarly affected at age 40, while his daughter is expected to develop symptoms earlier and more severely. The molecular basis for this increasing severity across generations is:
- A Expansion of CTG repeats during oogenesis
- B Expansion of CGG repeats during oogenesis
- C Expansion of CAG repeats during spermatogenesis ✓
- D Somatic expansion limited to the striatum
Explanation
Huntington disease results from expansion of a CAG trinucleotide repeat in the HTT gene encoding polyglutamine stretches in huntingtin. Anticipation occurs because large expansions arise preferentially during spermatogenesis, so paternal transmission produces markedly larger repeats and juvenile-onset disease in offspring. CGG expansion in FMR1 causes fragile X, where anticipation operates through maternal transmission, and CTG expansion in DMPK causes myotonic dystrophy. Somatic instability contributes to tissue pathology but does not explain intergenerational worsening.
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.