A c.3037G>A mutation in FBN1 gene causing Marfan syndrome with an atypically severe phenotype

Area of Science:

• Genetics
• Molecular Biology
• Cardiology

Background:

• Marfan syndrome is an autosomal dominant connective tissue disorder.
• It is primarily caused by mutations in the FBN1 gene, encoding fibrillin-1.
• Fibrillin-1 is essential for microfibril formation and connective tissue integrity.

Observation:

• A case of Marfan syndrome presented with severe ocular and systemic manifestations, including cardiac anomalies.
• Clinical diagnosis was confirmed by identifying a specific c.3037G>A mutation in the FBN1 gene.
• Molecular modeling revealed the mutation's impact on a calcium-dependent epidermal growth factor-like domain of fibrillin-1.

Findings:

• The identified FBN1 gene mutation (c.3037G>A) is associated with severe Marfan syndrome phenotypes.
• The mutation disrupts the calcium-dependent structure of a critical fibrillin-1 domain.
• This disruption affects microfibrillar formation, leading to connective tissue abnormalities.

Implications:

• Early clinical and molecular diagnosis of Marfan syndrome is vital.
• Prompt multidisciplinary assessment and monitoring are essential to prevent severe cardiac and ocular complications.
• Understanding the molecular basis of FBN1 mutations aids in predicting disease severity and guiding management.