Marfan syndrome is an autosomal dominant connective tissue disorder caused by a defect in the FBN1 gene on chromosome 15 encoding which protein?

• A. Fibrillin-1
• B. Collagen type I
• C. Elastin
• D. Laminin

Answer: (A)

The main point is that Marfan syndrome arises from a defect in a gene that encodes a major extracellular matrix glycoprotein critical for elastic fiber formation. The gene on chromosome 15, FBN1, encodes fibrillin-1, which assembles into microfibrils that form the scaffold for elastin in many connective tissues. When fibrillin-1 is faulty, elastic fibers become weak, leading to the characteristic tall habitus, arachnodactyly, and especially vascular (aortic root dilatation) and ocular (lens subluxation) issues seen in Marfan. Additionally, defective fibrillin-1 disrupts sequestration of TGF-β in the extracellular matrix, contributing to the tissue fragility. Other options refer to different proteins: collagen type I is a primary structural component of bone and dermis unrelated to FBN1; elastin is a separate protein encoded by a different gene and forms the elastic fibers; laminin is a basement membrane component. Therefore, the protein encoded by FBN1 is fibrillin-1.