A 5-year-old boy has progressive proximal muscle weakness, Gowers sign, and markedly elevated creatine kinase (15,000 U/L). Muscle biopsy shows absent dystrophin staining. His elder maternal cousin had similar symptoms and died at age 19. Genetic testing reveals a deletion of exons 45 to 50 in the DMD gene. According to the reading frame rule, how would this mutation be expected to affect phenotype severity?

• A Becker phenotype because any deletion in the DMD gene causes a milder disease
• B Duchenne phenotype because the deletion disrupts the reading frame
• C Becker phenotype because the deletion preserves the reading frame ✓
• D Duchenne phenotype because deletions are always more severe than duplications

Explanation

The reading frame rule (Monaco hypothesis) states that mutations disrupting the dystrophin reading frame cause Duchenne muscular dystrophy (no functional dystrophin), whereas in-frame deletions preserve the reading frame and produce Becker muscular dystrophy (truncated but partially functional dystrophin). C deletion of exons 45 to 50 removes 6 exons; if the number of deleted nucleotides is divisible by three, the reading frame is preserved, predicting a Becker phenotype.

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.