COL1A2 (p.Gly322Ser) Mutation Causes Late-Onset Osteogenesis Imperfecta: A Case Report

Area of Science:

• Genetics
• Orthopedics
• Pediatrics

Background:

• Osteogenesis Imperfecta (OI) is a group of genetic disorders characterized by bone fragility and low bone mass.
• OI presents with a wide clinical spectrum, from lethal in-utero forms to milder presentations.
• Manifestations typically decrease in severity with age.

Observation:

• A previously healthy 12-year-old male experienced a spontaneous femur fracture without preceding trauma.
• Physical examination revealed subtle grayish sclera; other systemic conditions and prior fractures were absent.
• Standard blood tests for calcium, phosphorus, vitamin D, BUN, creatinine, and PTH were within normal limits.

Findings:

• Genetic analysis identified a pathogenic COL1A2 mutation (c.964G>A [p.Gly322Ser]).
• This mutation confirmed the diagnosis of Osteogenesis Imperfecta.
• The patient's first symptom at age 12 indicates a late-onset presentation of OI.

Implications:

• This case underscores the possibility of late-onset OI, even in individuals without a prior history of fractures or bone deformities.
• Genetic testing is crucial for diagnosing OI, especially in atypical presentations.
• Understanding the genetic basis of OI, like COL1A2 mutations, aids in diagnosis and potential future therapeutic strategies.