A 19-year-old man has recurrent fractures after minimal trauma, blue sclerae, hearing loss, and dental enamel defects. Family history reveals autosomal dominant inheritance across three generations. The molecular defect involves which protein?

• A Type I collagen ✓
• B Type II collagen
• C Fibrillin-1
• D Osteocalcin

Explanation

Osteogenesis imperfecta, or brittle bone disease, results from mutations affecting type I collagen, most commonly in the COL1B1 or COL1B2 genes encoding its alpha chains. Blue sclerae occur because the thin sclera allows the underlying choroid to show through, and dentin defects produce the teeth abnormality. Type II collagen mutations cause spondyloepiphyseal dysplasias, fibrillin-1 defects cause Marfan syndrome, and osteocalcin is a bone matrix protein whose deficiency does not produce this 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.