Which extracellular matrix protein is defective in Marfan syndrome?

Which extracellular matrix protein is defective in Marfan syndrome?

• A. Elastin
• B. Laminin
• C. Collagen
• D. Fibrillin

Answer: (D)

Fibrillin-1 is the extracellular matrix glycoprotein that forms microfibrils in connective tissue, scaffolding elastic fibers and helping regulate TGF-beta signaling. In Marfan syndrome, mutations in the FBN1 gene produce abnormal fibrillin-1, so microfibrils form poorly. This weakens elastic connective tissue throughout the body, especially in the aorta, eyes, and skeleton. The aortic media becomes prone to dilation and dissection; the lens-supporting zonules can loosen, causing lens subluxation; and dysregulated TGF-beta signaling contributes to tall stature, long limbs, scoliosis, and other features. The other ECM components—elastin provides elasticity within fibers, collagen provides tensile strength, and laminin is a basement membrane component—do not explain the systemic connective-tissue manifestations seen in Marfan.

Fibrillin-1 is the extracellular matrix glycoprotein that forms microfibrils in connective tissue, scaffolding elastic fibers and helping regulate TGF-beta signaling. In Marfan syndrome, mutations in the FBN1 gene produce abnormal fibrillin-1, so microfibrils form poorly. This weakens elastic connective tissue throughout the body, especially in the aorta, eyes, and skeleton. The aortic media becomes prone to dilation and dissection; the lens-supporting zonules can loosen, causing lens subluxation; and dysregulated TGF-beta signaling contributes to tall stature, long limbs, scoliosis, and other features. The other ECM components—elastin provides elasticity within fibers, collagen provides tensile strength, and laminin is a basement membrane component—do not explain the systemic connective-tissue manifestations seen in Marfan.