Huntington disease is an autosomal dominant disorder caused by CAG trinucleotide repeat expansion in the HTT gene on chromosome 4p16.3. A 55-year-old man is affected. His 28-year-old son is asymptomatic but requests predictive testing. The son is found to have 44 CAG repeats. Which statement best describes anticipation in this disease?
- A Anticipation is most pronounced when the expanded allele is transmitted by the father ✓
- B Anticipation occurs only when the mutant allele is transmitted by the mother
- C Anticipation does not occur in Huntington disease because it is an autosomal dominant disease
- D Anticipation affects maternal and paternal transmission equally
Correct answer: A. Anticipation is most pronounced when the expanded allele is transmitted by the father
Explanation
In Huntington disease, CAG repeats are unstable during spermatogenesis and tend to expand further when transmitted paternally, leading to anticipation (earlier onset and increased severity in offspring). This contrasts with myotonic dystrophy and Fragile X syndrome, where maternal transmission drives the major expansion. Paternal anticipation in Huntington disease is a well-established and frequently examined concept.
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.