Trinucleotide repeat expansion causing disease by a toxic gain-of-function RNA mechanism (rather than loss of protein function) is best exemplified by:

• A Myotonic dystrophy type 1 (DMPK CTG expansion in 3' UTR) ✓
• B Fragile X syndrome (FMR1 CGG expansion)
• C Huntington disease (HTT CAG expansion)
• D Friedreich ataxia (FXN GAA expansion in intron)

Explanation

Myotonic dystrophy type 1 is caused by CTG expansion in the 3' UTR of DMPK gene. The expanded CUG repeat RNA accumulates in nuclear foci and sequesters RNA-binding proteins (MBNL1), causing aberrant alternative splicing of multiple downstream targets — a toxic RNA gain-of-function. Huntington's uses toxic expanded polyglutamine protein gain-of-function; Fragile X causes methylation-induced silencing (loss of FMRP); Friedreich ataxia causes frataxin silencing via heterochromatin.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.